The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)
University of Bristol · Academic
In term In term in the September 2026 edition: the latest version runs to 21 February 2028.
- Reference
- DARS-NIC-166879-K4Z0S
- Current version
- v3.3
- Term of current version
- 23 January 2026 to 21 February 2028
- Start date
- 10 December 2020
- Data controller
- Joint Data Controller
- Commercial purposes
- No
- Sublicensing
- No
- Files released to date
- 61
Data controllers
Why the data was released
Objective for processing
End-stage kidney disease (ESKD) affects around 55,000 people in the UK, with around 7,000 newly affected people each year. The survival probability at one, three and five years is around 90, 70 and 50%, respectively. Morbidity is high, with dialysis patients in the UK spending around 15 days in hospital per year. Quality of life on dialysis is also well below that of the general population. There is therefore an unmet and urgent need to improve ESKD patient treatment. Renal replacement therapy (dialysis or transplantation) is necessary when approximately 90% of kidney function is lost. Currently around 90% of existing dialysis patients are on some form of haemodialysis (HD) or haemodiafiltration (HDF). Although HD and HDF can be performed at home, the majority is performed in-centre.
Most people with kidney failure receive blood cleaning treatment (HD) 3 times a week at a hospital or clinic. Adding filtration (the removal and replacement of fluid) to regular HD (which allows toxins to leave the blood with minimal fluid removal/ replacement) results in HDF. As far as the patient is concerned, the two procedures are very similar – they both involve about 4 hours treatment 3 times a week, the dialysis machine is just set up slightly differently. HDF does, however, require a greater volume of high quality water at an increased cost to the NHS and the environment. By removing toxins more effectively, HDF should in theory have benefits, especially if high volumes are used (i.e. more than 21L of water removed and replaced per dialysis session). On the downside, such volumes of filtration could remove essential proteins from the blood stream or introduce toxins or infections from the water supply.
For patients with ESKD who are suitable for kidney transplantation the average waiting time in the UK is 2.8 years. Minimising damage from ESKD during this time is likely to improve their long-term outcomes. For others, kidney transplantation is not an option and quality and quantity of life needs to be optimised. The high-volume HDF vs high-flux HD registry trial (H4RT) is important to patients and the public because existing evidence suggests there may be up to a 40% reduction in mortality if patients receive high-volume HDF. This evidence is weak though, as patients have not previously been randomised to high-volume HDF vs high-flux HD, so the survival advantage may represent the fact that patients who achieve high-volume HDF are fitter. Despite a lack of strong evidence regarding increased patient benefit and cost-effectiveness, around 15% of patients in the UK are currently receiving HDF, with wide centre variation and plans for further adoption. Before this technology diffuses more widely across the UK, a definitive trial is needed to determine whether HDF should be made available to all patients, certain sub-groups of patients, or none.
The H4RT is therefore randomly allocating ESKD patients into either intervention (high-volume HDF) or control (high-flux HD) groups. Patients are 18 or over, and already attending a dialysis unit for maintenance HD or HDF 3 or more times a week in one of 235 possible dialysis units across the UK. Recruitment commenced 1st November 2017 and is ongoing, with funding currently approved until 31st August 2021. All patients have been provided with information about the nature of the trial and how their personal and sensitive data will be processed. Ethical issues have been considered and appropriately addressed, and there are no further issues anticipated. Patients with lack of capacity to consent; predicted life expectancy of less than 3 months; scheduled transition to living kidney donor transplant or home dialysis within 3 months; lack of clinical suitability for HDF; or who started maintenance HD or HDF within 4 weeks are excluded from the trial.
The primary outcome of the trial will be the determination of any difference between high-volume HDF and high-flux HD in terms of non-cancer mortality, and hospital admission due to a cardiovascular event or infection. The secondary outcomes will be the understanding of the impact of high-volume HDF on: cause specific and all causes of mortality; quality of life (generic, health utility, disease-specific and time to recover following dialysis); indirect effects such as inflammation, anaemia and bone mineral disorder management; and NHS costs/ cost-effectiveness (incremental cost per quality adjusted life year).
H4RT was funded on the basis of its "efficient study design", with baseline data collected by research nurses and all follow up being done through (1) linkage with routine healthcare data and (2) centrally administered patient quality of life questionnaires. The move to efficient study designs is in response to a recognition that randomised controlled trials have become very expensive in recent years, making them only affordable when there is a new product being tested with potential to generate profit under a patent. In efficient studies, there are no research visits after the baseline visit, and all subsequent data is collected by mailed/ emailed quality of life questionnaires and linkage to routine healthcare databases.
Data are needed at the individual patient level to follow up each patient in the trial. The University of Bristol will send a cohort including patient identifying information to NHS England for linkage, and NHS England will return the linked data in a pseudonymised form, providing many of the primary and secondary outcomes for the trial:
• Hospital Episode Statistics – Admitted Patient Care. This is required to derive part of the composite primary outcome, hospital admissions due to cardiovascular and infection events.
• Hospital Episode Statistics – Critical Care. This is required for the heath economics analysis, as admission to intensive care increases hospital admission costs considerably and HDF could influence cardiovascular and infection events that would lead to critical care admission.
• Hospital Episode Statistics – Outpatients. This is required for the health economics analysis, as HDF could influence cardiovascular and infection events that would lead to additional outpatient attendances.
• Civil Registration (Deaths) Secondary Care Cut & Civil Registrations of Death – This is required to derive the composite primary outcome, non-cancer mortality.
Pseudonymisation minimises the risk of sensitive clinical data on an individual patient being intercepted and traced to them. There are no alternative, less intrusive ways to collect the follow up data for this trial. These data will be combined with the baseline data collected by research nurses in a secure environment at the University of Bristol to compare the effectiveness of the two treatments. NHS England data will be required for each patient from their individual trial start date, between 2017-2022, until the end of the study, anticipated 2024.
Only data items necessary for the analysis to derive the primary and secondary outcomes have been requested. Data has been further minimised by requesting only NHS England data for each patient from the date they joined the trial.
Purpose of processing:
HES and Mortality data will be processed to derive the primary outcome and secondary outcomes for the trial following a statistical analysis plan which has been developed and will be signed off by the trial management group.
The primary objectives will be to determine the relative effectiveness of high-volume HDF compared with high-flux HD on the first event of non-cancer mortality, hospital admission due to a cardiovascular event or infection (primary outcome).
The secondary objectives are to determine the effect of high-volume HDF on:
• Mortality: from all-causes as well as cause specific
• Morbidity: hospital admissions related to cardiovascular events and infection events
• Quality of life: generic, health utility, disease-specific and time to recover following dialysis
• Indirect effects: laboratory indicators of inflammation, anaemia, bone mineral disorder management
• NHS costs and cost-effectiveness: incremental cost per quality-adjusted life year gained
The joint data controllers are the University of Bristol and North Bristol NHS Trust. The data will be processed at Bristol Randomised Trials Collaboration which is part of the University of Bristol. The Chief Investigator and all co-investigators accessing NHS England data are substantive employees of the University of Bristol.
The lawful basis for processing personal data for the H4RT are Articles 6(1)(e) and 9(2)(j) of the General Data Protection Regulation (2018). These lawful bases can be justified as follows:
Article 6(1)(e), i.e. that the processing is being undertaken as a 'public task': H4RT is an NIHR HTA competitively funded, peer-reviewed randomised controlled trial. It is being Sponsored by an NHS organisation (North Bristol NHS Trust) and delivered by a UK Higher Education Institute (University of Bristol).
Article 9(2)(j), i.e. that the processing is being undertaken in the 'public interest': The need for better evidence on the effectiveness of high-volume HDF to inform NHS care was recognised and prioritised by NIHR (and has subsequently been recognised by NICE). Data is only being processed on participants in the trial, who have all had the research (including the linkage of their trial data with routine healthcare databases) explained to them in an approved patient information sheet by a research nurse with Good Clinical Practice training. All current guidance has been followed to mitigate risk from data processing to participants. There will be no processing of data on members of the public who have not provided consent to take part in the trial.
Both North Bristol NHS Trust and the University of Bristol therefore have a public interest to undertake such processing of personal and sensitive data to advance the evidence base for clinical care and drive improvements in patient survival, hospitalisation and quality of life on dialysis.
The UK Renal Registry will be providing data to the University of Bristol on advanced chronic kidney disease outcomes. Members of the study team, including the chief investigator, were previously part funded by UKRR but employed by NHS. These employees are no longer being funded by UKRR and UKRR is not acting as a data processor.
UK health Security Agency will be asked to provide data to the University of Bristol for infections they collect, such as methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus.
The funder is NIHR Health Technology Assessment. NIHR do not determine the purpose or the manner in which the data will be processed.
Processing activities
Good clinical practice-trained research staff provide eligible patients with information about the trial in the form of a participant information sheet. If the patient agrees to participate, they complete and sign a consent form. The research nurse completes paper forms containing (a) administrative data (with identifying information) and (b) clinical data. These documents are returned securely (by recorded delivery in tamper proof envelopes) to the Bristol Randomised Trials Collaboration (BRTC) unit at the University of Bristol.
The trial administrator and trial manager at the University of Bristol receive the paper documents from the recruiting sites and enter them into either the administrative or clinical database. The two databases are kept separate and would not be re-linked.
Patient clinical data is pseudonymised with unique study IDs. Email addresses are collected with the clinical data as they are essential for the correct functioning of a required survey feature. The ‘Email Address’ field is flagged as an identifier and not included in the export for the statistician, so the data set can be considered pseudonymised at export and does not need further processing. Further pseudonymised clinical data from the UK Renal Registry, UK Health Security Agency, and trial case report forms and patient questionnaires collected by researchers at the recruiting sites, is added to the clinical database over the course of the trial.
The pseudonymised data will include only those records for each patient that occur on or after the patient's start date.
METHODOLOGY
- The University of Bristol will send a file containing identifiable study cohort data to NHS England.
The cohort will contain the Study ID, NHS Number, Date of Birth, and Gender. No special category data, specifically no health data, will be sent from the University of Bristol.
- NHS England will link the study cohort records to HES Outpatients, Critical Care, Admitted Patient Care and mortality data sets. A pseudonymised file containing the pseudonym study IDs and health data for the study cohort will then be returned to the University of Bristol.
- This will then be linked using the pseudonym study IDs to the other clinical data already held by the University of Bristol. The record level personal data provided to the University of Bristol by NHS England, UK Renal Registry and UK Health Security Agency will remain at the University of Bristol and will not be released to any other organisations, unless in the form of aggregated, suppressed data in line with the HES analysis guide.
The pseudonymised clinical dataset will be held on a dedicated server storing only H4RT data in one of two secure data centres. These centres have physical and network security measures in place including a firewall set to only allow access only from specific static IP addresses over specific ports. This means that only machines registered by the persons responsible for the data and configured by IT Services will be allowed to gain access to this information. The University of Bristol statisticians analysing the NHS England data do not also have access to the administrative database containing patient identifiable information. The trial manager and trial administrator have access to both databases to deposit clinical information, however there will be no requirement or attempt to re-identify individuals. Data processing will only be carried out by substantive employees of the data processor who have been appropriately trained in data protection and confidentiality.
HES DISCLOSURE CONTROL / SMALL NUMBER SUPPRESSION
In order to protect patient confidentiality, when presenting results calculated from HES record level data, outputs will contain only aggregate level data with small numbers suppressed in line with HES Analysis Guide. When publishing HES data, organisation must make sure that:
· cell values from 1 to 7 are suppressed at a local level to prevent possible identification of individuals from small counts within the table.
· Zeros (0) do not need to be suppressed.
· All other counts will be rounded to the nearest 5.
Data will not be made available to any third parties other than those specified except in the form of aggregated outputs with small numbers suppressed in line with the HES Analysis Guide.
Expected output
Study progress and results will be disseminated through the existing communication channels of the UK Renal Registry and the UK Renal Association via newsletters to the renal community. Both have active twitter accounts with more than 3,000 followers. Newsletters and social media accounts at the University of Bristol and North Bristol NHS Trust will additionally be used to disseminate and publicise the study progress and results. An H4RT twitter account has been set up to keep interested patients, carers, clinicians, managers and policy makers up-to-date with trial progress. Representatives from the Kidney Care UK and National Kidney Federation will also use their established channels for communicating the progress and findings of the study to patients such as regular newsletters, active social media accounts, a network of kidney patient associations and annual meetings.
Abstracts for posters and/ or oral presentations will be submitted to national and international conferences, such as UK Kidney Week, ERA-EDTA, American Society of Nephrology and World Congress of Nephrology (estimated 2024).
Peer-reviewed publications will include:
1. Methods paper. Once finalised (estimated Dec 2021), the protocol will be published in an open access academic journal.
2. Main results paper. The primary analysis is expected to occur in Autumn 2025, with the main paper being submitted for publication in Spring 2026. With the key findings likely to be practice changing and of interest to a wide range of clinicians and policy makers, they will be of interest to high impact journals such as the BMJ, the New England Journal of Medicine and the Journal of the American Medical Association. The Bristol Randomised Trials Collaboration has a track record of publishing output from its complex trials in high impact clinical journals and highly respected methodological journals.
Two public and patient involvement (PPI) groups: the Patient Council and local Kidney Patient Association - both comprising 15-20 dialysis and former dialysis/ transplant patients, guided the objectives of this study. Patients wanted to know whether HDF improves survival, symptoms and quality of life, and whether it is safe. Some raised concerns about its environmental impact. A PPI co-applicant helped draft elements of the study protocol. Patients and the public remain active in the running of the trial through the steering committee and patient advisory group. The latter involves annual – biannual meetings where progress and results from the study are presented and patient interpretation sought. Patients in the group then advise on the best way to disseminate the study findings to other patients, including the production of plain English summaries that will be used by patients and carers to assist them in making evidence based treatment decisions and further developing dissemination policy.
The funder (NIHR) requires sight of all output before it is made public (with the exception of individual tweets). The trial management group (chaired by the chief investigator, Fergus Caskey) will determine the dissemination strategy, with approval by the Sponsor (North Bristol NHS Trust) and trials unit (University of Bristol).
Data will only be published in anonymised, aggregate form in line with the HES Analysis Guide.
Expected measurable benefits
The benefits from this dissemination will not be realised for health care until the main results of the trial are published in 2026:
- If HDF proves safe and effective at improving survival and/ or quality of life, it is likely to become the main form of HD in the UK, Europe and even the USA. Trial publications could result in changing NICE recommendations (the trial has already led to NICE changing its draft recommendation on HDF in 2018) and associated Renal Association guidance. This in turn would change medical practice, with renal units gradually converting their machines and consumables to be able to provide HDF to all patients. This will lead to improved outcomes for people with end-stage kidney disease – 25,000 people in the UK at the moment and 2 million people worldwide. If the estimates from post-hoc analyses of prior trials are correct, HDF could reduce mortality on dialysis by up to 40%.
- If HDF proves unsafe or ineffective, the renal units in Europe that have been adopting it before evidence of safety/ effectiveness exist will need to reconsider this (and probably revert to the current standard, high-flux HD). This will lead to reduced harm (from unsafe HDF) and/ or a reduced economic and environmental cost from HDF (i.e. 6,000L of water per patient per year). It will also refocus efforts by dialysis innovators to look for new ways of delivering dialysis that actually do lead to improvements in survival.
Depending on whether the trial shows a benefit from high-volume HDF or not, the beneficiaries will be:
1/ patients – who will either have a reduced risk of dying on dialysis or more efforts put into developing new dialysis technologies that will extend their lives/ improve their quality of life
2/ healthcare economies – who may be able to negotiate lower cost contracts for delivering HD if they do not have to pay for HDF
3/ the environment – with 6,000L less water being used per patient per year.
This is not expected to be seen until after the results of the trial in 2026.
Benefits reported so far
NHS data provided to date has been used to prepare the statistical code to clean and analyse the final shared data set, i.e., to speed up analysis once the full shared dataset is available. The Data Controller, in randomised controlled trials, is not allowed to look at outcomes data prior to closing the dataset for final analysis. This is to avoid premature interpretations of efficacy or futility which could interfere with the trials ability to deliver of an unbiased, robust conclusion that would change practice. External facing yielded benefit has therefore been limited.
Datasets on the current version
Legal basis for provision: Health and Social Care Act 2012 – s261(2)(c); National Health Service Act 2006 - s251 - 'Control of patient information'.; Health and Social Care Act 2012 – s261(2)(c)
| Dataset | Type of data | Sensitivity | Frequency | Confidential data |
|---|---|---|---|---|
| Civil Registrations of Death | Identifiable | Sensitive | One-Off | Consent (Reasonable Expectation) |
| Civil Registrations of Death - Secondary Care Cut | Identifiable | Sensitive | Ongoing | Consent (Reasonable Expectation) |
| HES:Civil Registration (Deaths) bridge | Identifiable | Non-Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Admitted Patient Care (HES APC) | Identifiable | Non-Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Critical Care (HES Critical Care) | Identifiable | Non-Sensitive | Ongoing | Consent (Reasonable Expectation) |
| Hospital Episode Statistics Outpatients (HES OP) | Identifiable | Non-Sensitive | Ongoing | Consent (Reasonable Expectation) |
Files released
Files released counts only files released externally by DARS. Access granted in NHS England's own systems, such as its Secure Data Environment, is not included.
Patient opt-outs were not applied to any of the 61 files released under this agreement, across every version. About opt-outs
Files released against version 3.3 of this agreement, summarised by dataset.
| Dataset | Files | First released | Last released | Opt-outs applied |
|---|---|---|---|---|
| Civil Registrations of Death | 2 | January 2026 | April 2026 | No |
Version history
The register lists each renewal of this agreement as a separate row. This site has 4 versions.
DARS-NIC-166879-K4Z0S-v3.3 23 January 2026 to 21 February 2028
- Title
- The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 6
- Files released
- 2
Datasets: Civil Registrations of Death; Civil Registrations of Death - Secondary Care Cut; HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP)
What changed from DARS-NIC-166879-K4Z0S-v2.2
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2026-01-23 | |
| End date | 2028-02-21 |
Datasets: + Civil Registrations of Death
Objective for processing
[10 paragraphs unchanged]
• Civil Registration (Deaths) Secondary Care Cut
& Civil Registrations of Death
– This is required to derive the composite primary outcome, non-cancer mortality.
[3 paragraphs unchanged]
HES and
Civil Registration
Mortality
data will be processed to derive the primary outcome and secondary outcomes
[10 words unchanged]
been developed and will be signed off by the trial management group.
[15 paragraphs unchanged]
Processing activities
[7 paragraphs unchanged]
- NHS England will link the study cohort records to HES Outpatients, Critical Care, Admitted Patient Care and
Civil Registrations (Deaths) Secondary Care Cut
mortality
data sets. A pseudonymised file containing the pseudonym study IDs and health data for the study cohort will then be returned to the University of Bristol.
[8 paragraphs unchanged]
Unchanged: Expected output, Expected measurable benefits, Benefits reported.
DARS-NIC-166879-K4Z0S-v2.2 2 July 2025 to 21 February 2026
- Title
- The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 5
- Files released
- 31
Datasets: Civil Registrations of Death - Secondary Care Cut; HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP)
What changed from DARS-NIC-166879-K4Z0S-v1.6
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2025-07-02 |
Processing activities
[3 paragraphs unchanged]
DATA PREVIOUSLY REQUESTED UNDER v0.19 OF THE DATA SHARING AGREEMENT
Pseudonymised record level 6 years of HES APC, CC, and OP linked to Deaths data - An initial historical drop of AR 2017/18, 2018/19, 2019/20, plus 2020/21 M07 at agreement sign-off and thereafter
a drop of AR 2020/21 in Sept/Oct 2021, and
a drop of AR 2021/22 in Sept/Oct 2022 and
a drop of AR 2022/23 in Sept/Oct 2023
[7 APYs dropped in 4 disseminations].
DATA TO BE DISSEMINATED UNDER V1.5
HES APC,CC and OP 22/23 annual data and deaths owing from the previous iteration v0.19 of the DSA. In addition in July 2025, HES APC, CC, OP 23/24 and 25/26 M02 data and mortality data, will be disseminated to align to the study end date.
[13 paragraphs unchanged]
Benefits reported
The only yielded benefits to date have been the ability of the trial statistician to start working on the first extract of the data to develop the code to clean and analyse the main extract as rapidly as possible in 2025 when follow up finishes and the trial needs to report. The ability to become familiar with the data and write the code will significantly reduce the time to presentation and publication of the main results.
NHS data provided to date has been used to prepare the statistical code to clean and analyse the final shared data set, i.e., to speed up analysis once the full shared dataset is available. The Data Controller, in randomised controlled trials, is not allowed to look at outcomes data prior to closing the dataset for final analysis. This is to avoid premature interpretations of efficacy or futility which could interfere with the trials ability to deliver of an unbiased, robust conclusion that would change practice. External facing yielded benefit has therefore been limited.
YIELDED BENEFITS UPDATE 2024
There have been no outputs through the processing of the data to date, but there were never intended to be. The data is being processed by the trials statisticians to develop the code that will be used for the main analysis of the second and final extraction of data when the trial follow up is complete (end May 2025.)
Unchanged: Objective for processing, Expected output, Expected measurable benefits.
Objective for processing
End-stage kidney disease (ESKD) affects around 55,000 people in the UK, with around 7,000 newly affected people each year. The survival probability at one, three and five years is around 90, 70 and 50%, respectively. Morbidity is high, with dialysis patients in the UK spending around 15 days in hospital per year. Quality of life on dialysis is also well below that of the general population. There is therefore an unmet and urgent need to improve ESKD patient treatment. Renal replacement therapy (dialysis or transplantation) is necessary when approximately 90% of kidney function is lost. Currently around 90% of existing dialysis patients are on some form of haemodialysis (HD) or haemodiafiltration (HDF). Although HD and HDF can be performed at home, the majority is performed in-centre.
Most people with kidney failure receive blood cleaning treatment (HD) 3 times a week at a hospital or clinic. Adding filtration (the removal and replacement of fluid) to regular HD (which allows toxins to leave the blood with minimal fluid removal/ replacement) results in HDF. As far as the patient is concerned, the two procedures are very similar – they both involve about 4 hours treatment 3 times a week, the dialysis machine is just set up slightly differently. HDF does, however, require a greater volume of high quality water at an increased cost to the NHS and the environment. By removing toxins more effectively, HDF should in theory have benefits, especially if high volumes are used (i.e. more than 21L of water removed and replaced per dialysis session). On the downside, such volumes of filtration could remove essential proteins from the blood stream or introduce toxins or infections from the water supply.
For patients with ESKD who are suitable for kidney transplantation the average waiting time in the UK is 2.8 years. Minimising damage from ESKD during this time is likely to improve their long-term outcomes. For others, kidney transplantation is not an option and quality and quantity of life needs to be optimised. The high-volume HDF vs high-flux HD registry trial (H4RT) is important to patients and the public because existing evidence suggests there may be up to a 40% reduction in mortality if patients receive high-volume HDF. This evidence is weak though, as patients have not previously been randomised to high-volume HDF vs high-flux HD, so the survival advantage may represent the fact that patients who achieve high-volume HDF are fitter. Despite a lack of strong evidence regarding increased patient benefit and cost-effectiveness, around 15% of patients in the UK are currently receiving HDF, with wide centre variation and plans for further adoption. Before this technology diffuses more widely across the UK, a definitive trial is needed to determine whether HDF should be made available to all patients, certain sub-groups of patients, or none.
The H4RT is therefore randomly allocating ESKD patients into either intervention (high-volume HDF) or control (high-flux HD) groups. Patients are 18 or over, and already attending a dialysis unit for maintenance HD or HDF 3 or more times a week in one of 235 possible dialysis units across the UK. Recruitment commenced 1st November 2017 and is ongoing, with funding currently approved until 31st August 2021. All patients have been provided with information about the nature of the trial and how their personal and sensitive data will be processed. Ethical issues have been considered and appropriately addressed, and there are no further issues anticipated. Patients with lack of capacity to consent; predicted life expectancy of less than 3 months; scheduled transition to living kidney donor transplant or home dialysis within 3 months; lack of clinical suitability for HDF; or who started maintenance HD or HDF within 4 weeks are excluded from the trial.
The primary outcome of the trial will be the determination of any difference between high-volume HDF and high-flux HD in terms of non-cancer mortality, and hospital admission due to a cardiovascular event or infection. The secondary outcomes will be the understanding of the impact of high-volume HDF on: cause specific and all causes of mortality; quality of life (generic, health utility, disease-specific and time to recover following dialysis); indirect effects such as inflammation, anaemia and bone mineral disorder management; and NHS costs/ cost-effectiveness (incremental cost per quality adjusted life year).
H4RT was funded on the basis of its "efficient study design", with baseline data collected by research nurses and all follow up being done through (1) linkage with routine healthcare data and (2) centrally administered patient quality of life questionnaires. The move to efficient study designs is in response to a recognition that randomised controlled trials have become very expensive in recent years, making them only affordable when there is a new product being tested with potential to generate profit under a patent. In efficient studies, there are no research visits after the baseline visit, and all subsequent data is collected by mailed/ emailed quality of life questionnaires and linkage to routine healthcare databases.
Data are needed at the individual patient level to follow up each patient in the trial. The University of Bristol will send a cohort including patient identifying information to NHS England for linkage, and NHS England will return the linked data in a pseudonymised form, providing many of the primary and secondary outcomes for the trial:
• Hospital Episode Statistics – Admitted Patient Care. This is required to derive part of the composite primary outcome, hospital admissions due to cardiovascular and infection events.
• Hospital Episode Statistics – Critical Care. This is required for the heath economics analysis, as admission to intensive care increases hospital admission costs considerably and HDF could influence cardiovascular and infection events that would lead to critical care admission.
• Hospital Episode Statistics – Outpatients. This is required for the health economics analysis, as HDF could influence cardiovascular and infection events that would lead to additional outpatient attendances.
• Civil Registration (Deaths) Secondary Care Cut – This is required to derive the composite primary outcome, non-cancer mortality.
Pseudonymisation minimises the risk of sensitive clinical data on an individual patient being intercepted and traced to them. There are no alternative, less intrusive ways to collect the follow up data for this trial. These data will be combined with the baseline data collected by research nurses in a secure environment at the University of Bristol to compare the effectiveness of the two treatments. NHS England data will be required for each patient from their individual trial start date, between 2017-2022, until the end of the study, anticipated 2024.
Only data items necessary for the analysis to derive the primary and secondary outcomes have been requested. Data has been further minimised by requesting only NHS England data for each patient from the date they joined the trial.
Purpose of processing:
HES and Civil Registration data will be processed to derive the primary outcome and secondary outcomes for the trial following a statistical analysis plan which has been developed and will be signed off by the trial management group.
The primary objectives will be to determine the relative effectiveness of high-volume HDF compared with high-flux HD on the first event of non-cancer mortality, hospital admission due to a cardiovascular event or infection (primary outcome).
The secondary objectives are to determine the effect of high-volume HDF on:
• Mortality: from all-causes as well as cause specific
• Morbidity: hospital admissions related to cardiovascular events and infection events
• Quality of life: generic, health utility, disease-specific and time to recover following dialysis
• Indirect effects: laboratory indicators of inflammation, anaemia, bone mineral disorder management
• NHS costs and cost-effectiveness: incremental cost per quality-adjusted life year gained
The joint data controllers are the University of Bristol and North Bristol NHS Trust. The data will be processed at Bristol Randomised Trials Collaboration which is part of the University of Bristol. The Chief Investigator and all co-investigators accessing NHS England data are substantive employees of the University of Bristol.
The lawful basis for processing personal data for the H4RT are Articles 6(1)(e) and 9(2)(j) of the General Data Protection Regulation (2018). These lawful bases can be justified as follows:
Article 6(1)(e), i.e. that the processing is being undertaken as a 'public task': H4RT is an NIHR HTA competitively funded, peer-reviewed randomised controlled trial. It is being Sponsored by an NHS organisation (North Bristol NHS Trust) and delivered by a UK Higher Education Institute (University of Bristol).
Article 9(2)(j), i.e. that the processing is being undertaken in the 'public interest': The need for better evidence on the effectiveness of high-volume HDF to inform NHS care was recognised and prioritised by NIHR (and has subsequently been recognised by NICE). Data is only being processed on participants in the trial, who have all had the research (including the linkage of their trial data with routine healthcare databases) explained to them in an approved patient information sheet by a research nurse with Good Clinical Practice training. All current guidance has been followed to mitigate risk from data processing to participants. There will be no processing of data on members of the public who have not provided consent to take part in the trial.
Both North Bristol NHS Trust and the University of Bristol therefore have a public interest to undertake such processing of personal and sensitive data to advance the evidence base for clinical care and drive improvements in patient survival, hospitalisation and quality of life on dialysis.
The UK Renal Registry will be providing data to the University of Bristol on advanced chronic kidney disease outcomes. Members of the study team, including the chief investigator, were previously part funded by UKRR but employed by NHS. These employees are no longer being funded by UKRR and UKRR is not acting as a data processor.
UK health Security Agency will be asked to provide data to the University of Bristol for infections they collect, such as methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus.
The funder is NIHR Health Technology Assessment. NIHR do not determine the purpose or the manner in which the data will be processed.
Expected output
Study progress and results will be disseminated through the existing communication channels of the UK Renal Registry and the UK Renal Association via newsletters to the renal community. Both have active twitter accounts with more than 3,000 followers. Newsletters and social media accounts at the University of Bristol and North Bristol NHS Trust will additionally be used to disseminate and publicise the study progress and results. An H4RT twitter account has been set up to keep interested patients, carers, clinicians, managers and policy makers up-to-date with trial progress. Representatives from the Kidney Care UK and National Kidney Federation will also use their established channels for communicating the progress and findings of the study to patients such as regular newsletters, active social media accounts, a network of kidney patient associations and annual meetings.
Abstracts for posters and/ or oral presentations will be submitted to national and international conferences, such as UK Kidney Week, ERA-EDTA, American Society of Nephrology and World Congress of Nephrology (estimated 2024).
Peer-reviewed publications will include:
1. Methods paper. Once finalised (estimated Dec 2021), the protocol will be published in an open access academic journal.
2. Main results paper. The primary analysis is expected to occur in Autumn 2025, with the main paper being submitted for publication in Spring 2026. With the key findings likely to be practice changing and of interest to a wide range of clinicians and policy makers, they will be of interest to high impact journals such as the BMJ, the New England Journal of Medicine and the Journal of the American Medical Association. The Bristol Randomised Trials Collaboration has a track record of publishing output from its complex trials in high impact clinical journals and highly respected methodological journals.
Two public and patient involvement (PPI) groups: the Patient Council and local Kidney Patient Association - both comprising 15-20 dialysis and former dialysis/ transplant patients, guided the objectives of this study. Patients wanted to know whether HDF improves survival, symptoms and quality of life, and whether it is safe. Some raised concerns about its environmental impact. A PPI co-applicant helped draft elements of the study protocol. Patients and the public remain active in the running of the trial through the steering committee and patient advisory group. The latter involves annual – biannual meetings where progress and results from the study are presented and patient interpretation sought. Patients in the group then advise on the best way to disseminate the study findings to other patients, including the production of plain English summaries that will be used by patients and carers to assist them in making evidence based treatment decisions and further developing dissemination policy.
The funder (NIHR) requires sight of all output before it is made public (with the exception of individual tweets). The trial management group (chaired by the chief investigator, Fergus Caskey) will determine the dissemination strategy, with approval by the Sponsor (North Bristol NHS Trust) and trials unit (University of Bristol).
Data will only be published in anonymised, aggregate form in line with the HES Analysis Guide.
Benefits reported
NHS data provided to date has been used to prepare the statistical code to clean and analyse the final shared data set, i.e., to speed up analysis once the full shared dataset is available. The Data Controller, in randomised controlled trials, is not allowed to look at outcomes data prior to closing the dataset for final analysis. This is to avoid premature interpretations of efficacy or futility which could interfere with the trials ability to deliver of an unbiased, robust conclusion that would change practice. External facing yielded benefit has therefore been limited.
DARS-NIC-166879-K4Z0S-v1.6 22 February 2024 to 21 February 2026
- Title
- The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 5
- Files released
- 7
Datasets: Civil Registrations of Death - Secondary Care Cut; HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP)
What changed from DARS-NIC-166879-K4Z0S-v0.19
Text removed is struck through; text added is underlined. Unchanged paragraphs are summarised rather than repeated.
| Field | Was | Became |
|---|---|---|
| Start date | 2024-02-22 | |
| End date | 2026-02-21 | |
| Civil Registrations of Death - Secondary Care Cut: type of data | Identifiable | |
| HES:Civil Registration (Deaths) bridge: type of data | Identifiable | |
| Hospital Episode Statistics Admitted Patient Care (HES APC): type of data | Identifiable | |
| Hospital Episode Statistics Critical Care (HES Critical Care): type of data | Identifiable | |
| Hospital Episode Statistics Outpatients (HES OP): type of data | Identifiable |
Objective for processing
[6 paragraphs unchanged]
Data are needed at the individual patient level to follow up each
[6 words unchanged]
of Bristol will send a cohort including patient identifying information to NHS
Digital
England
for linkage, and NHS
Digital
England
will return the linked data in a pseudonymised form, providing many of the primary and secondary outcomes for the trial:
[4 paragraphs unchanged]
Pseudonymisation minimises the risk of sensitive clinical data on an individual patient
[41 words unchanged]
University of Bristol to compare the effectiveness of the two treatments. NHS
Digital
England
data will be required for each patient from their individual trial start date, between 2017-2022, until the end of the study, anticipated 2024.
Only data items necessary for the analysis to derive the primary and secondary outcomes have been requested. Data has been further minimised by requesting only NHS
Digital
England
data for each patient from the date they joined the trial.
[9 paragraphs unchanged]
The joint data controllers are the University of Bristol and North Bristol
[16 words unchanged]
the University of Bristol. The Chief Investigator and all co-investigators accessing NHS
Digital
England
data are substantive employees of the University of Bristol.
[5 paragraphs unchanged]
Public Health England
UK health Security Agency
will be asked to provide data to the University of Bristol for infections they collect, such as methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus.
[1 paragraph unchanged]
Processing activities
[2 paragraphs unchanged]
Patient clinical data is pseudonymised with unique study IDs. Email addresses are
[49 words unchanged]
need further processing. Further pseudonymised clinical data from the UK Renal Registry,
Public
UK
Health
England,
Security Agency,
and trial case report forms and patient questionnaires collected by researchers at the recruiting sites, is added to the clinical database over the course of the trial.
DATA REQUESTED
DATA PREVIOUSLY REQUESTED UNDER v0.19 OF THE DATA SHARING AGREEMENT
[3 paragraphs unchanged]
a drop of AR
2021/22
2022/23
in Sept/Oct 2023
[1 paragraph unchanged]
DATA TO BE DISSEMINATED UNDER V1.5
HES APC,CC and OP 22/23 annual data and deaths owing from the previous iteration v0.19 of the DSA. In addition in July 2025, HES APC, CC, OP 23/24 and 25/26 M02 data and mortality data, will be disseminated to align to the study end date.
[2 paragraphs unchanged]
- The University of Bristol will send a file containing identifiable study cohort data to NHS
Digital.
England.
[1 paragraph unchanged]
- NHS
Digital
England
will link the study cohort records to HES Outpatients, Critical Care, Admitted
[23 words unchanged]
the study cohort will then be returned to the University of Bristol.
- This will then be linked using the pseudonym study IDs to
[12 words unchanged]
record level personal data provided to the University of Bristol by NHS
Digital,
England,
UK Renal Registry and
Public
UK
Health
England
Security Agency
will remain at the University of Bristol and will not be released
[7 words unchanged]
form of aggregated, suppressed data in line with the HES analysis guide.
The pseudonymised clinical dataset will be held on a dedicated server storing
[60 words unchanged]
access to this information. The University of Bristol statisticians analysing the NHS
Digital
England
data do not also have access to the administrative database containing patient
[40 words unchanged]
data processor who have been appropriately trained in data protection and confidentiality.
[1 paragraph unchanged]
In order to protect patient confidentiality, when presenting results calculated from HES
[12 words unchanged]
numbers suppressed in line with HES Analysis Guide. When publishing HES data,
you
organisation
must make sure that:
[4 paragraphs unchanged]
Expected output
[4 paragraphs unchanged]
2. Main results paper. The primary analysis is expected to occur in
Spring 2024,
Autumn 2025,
with the main paper being submitted for publication in
Summer 2024.
Spring 2026.
With the key findings likely to be practice changing and of interest
[50 words unchanged]
complex trials in high impact clinical journals and highly respected methodological journals.
[3 paragraphs unchanged]
Expected measurable benefits
The benefits from this dissemination will not be realised for health care until the main results of the trial are published in
2024:
2026:
[6 paragraphs unchanged]
This is not expected to be seen until after the results of the trial in
2024.
2026.
Benefits reported
Yielded Benefits is not a requirement for new applications.
The only yielded benefits to date have been the ability of the trial statistician to start working on the first extract of the data to develop the code to clean and analyse the main extract as rapidly as possible in 2025 when follow up finishes and the trial needs to report. The ability to become familiar with the data and write the code will significantly reduce the time to presentation and publication of the main results.
YIELDED BENEFITS UPDATE 2024
There have been no outputs through the processing of the data to date, but there were never intended to be. The data is being processed by the trials statisticians to develop the code that will be used for the main analysis of the second and final extraction of data when the trial follow up is complete (end May 2025.)
Objective for processing
End-stage kidney disease (ESKD) affects around 55,000 people in the UK, with around 7,000 newly affected people each year. The survival probability at one, three and five years is around 90, 70 and 50%, respectively. Morbidity is high, with dialysis patients in the UK spending around 15 days in hospital per year. Quality of life on dialysis is also well below that of the general population. There is therefore an unmet and urgent need to improve ESKD patient treatment. Renal replacement therapy (dialysis or transplantation) is necessary when approximately 90% of kidney function is lost. Currently around 90% of existing dialysis patients are on some form of haemodialysis (HD) or haemodiafiltration (HDF). Although HD and HDF can be performed at home, the majority is performed in-centre.
Most people with kidney failure receive blood cleaning treatment (HD) 3 times a week at a hospital or clinic. Adding filtration (the removal and replacement of fluid) to regular HD (which allows toxins to leave the blood with minimal fluid removal/ replacement) results in HDF. As far as the patient is concerned, the two procedures are very similar – they both involve about 4 hours treatment 3 times a week, the dialysis machine is just set up slightly differently. HDF does, however, require a greater volume of high quality water at an increased cost to the NHS and the environment. By removing toxins more effectively, HDF should in theory have benefits, especially if high volumes are used (i.e. more than 21L of water removed and replaced per dialysis session). On the downside, such volumes of filtration could remove essential proteins from the blood stream or introduce toxins or infections from the water supply.
For patients with ESKD who are suitable for kidney transplantation the average waiting time in the UK is 2.8 years. Minimising damage from ESKD during this time is likely to improve their long-term outcomes. For others, kidney transplantation is not an option and quality and quantity of life needs to be optimised. The high-volume HDF vs high-flux HD registry trial (H4RT) is important to patients and the public because existing evidence suggests there may be up to a 40% reduction in mortality if patients receive high-volume HDF. This evidence is weak though, as patients have not previously been randomised to high-volume HDF vs high-flux HD, so the survival advantage may represent the fact that patients who achieve high-volume HDF are fitter. Despite a lack of strong evidence regarding increased patient benefit and cost-effectiveness, around 15% of patients in the UK are currently receiving HDF, with wide centre variation and plans for further adoption. Before this technology diffuses more widely across the UK, a definitive trial is needed to determine whether HDF should be made available to all patients, certain sub-groups of patients, or none.
The H4RT is therefore randomly allocating ESKD patients into either intervention (high-volume HDF) or control (high-flux HD) groups. Patients are 18 or over, and already attending a dialysis unit for maintenance HD or HDF 3 or more times a week in one of 235 possible dialysis units across the UK. Recruitment commenced 1st November 2017 and is ongoing, with funding currently approved until 31st August 2021. All patients have been provided with information about the nature of the trial and how their personal and sensitive data will be processed. Ethical issues have been considered and appropriately addressed, and there are no further issues anticipated. Patients with lack of capacity to consent; predicted life expectancy of less than 3 months; scheduled transition to living kidney donor transplant or home dialysis within 3 months; lack of clinical suitability for HDF; or who started maintenance HD or HDF within 4 weeks are excluded from the trial.
The primary outcome of the trial will be the determination of any difference between high-volume HDF and high-flux HD in terms of non-cancer mortality, and hospital admission due to a cardiovascular event or infection. The secondary outcomes will be the understanding of the impact of high-volume HDF on: cause specific and all causes of mortality; quality of life (generic, health utility, disease-specific and time to recover following dialysis); indirect effects such as inflammation, anaemia and bone mineral disorder management; and NHS costs/ cost-effectiveness (incremental cost per quality adjusted life year).
H4RT was funded on the basis of its "efficient study design", with baseline data collected by research nurses and all follow up being done through (1) linkage with routine healthcare data and (2) centrally administered patient quality of life questionnaires. The move to efficient study designs is in response to a recognition that randomised controlled trials have become very expensive in recent years, making them only affordable when there is a new product being tested with potential to generate profit under a patent. In efficient studies, there are no research visits after the baseline visit, and all subsequent data is collected by mailed/ emailed quality of life questionnaires and linkage to routine healthcare databases.
Data are needed at the individual patient level to follow up each patient in the trial. The University of Bristol will send a cohort including patient identifying information to NHS England for linkage, and NHS England will return the linked data in a pseudonymised form, providing many of the primary and secondary outcomes for the trial:
• Hospital Episode Statistics – Admitted Patient Care. This is required to derive part of the composite primary outcome, hospital admissions due to cardiovascular and infection events.
• Hospital Episode Statistics – Critical Care. This is required for the heath economics analysis, as admission to intensive care increases hospital admission costs considerably and HDF could influence cardiovascular and infection events that would lead to critical care admission.
• Hospital Episode Statistics – Outpatients. This is required for the health economics analysis, as HDF could influence cardiovascular and infection events that would lead to additional outpatient attendances.
• Civil Registration (Deaths) Secondary Care Cut – This is required to derive the composite primary outcome, non-cancer mortality.
Pseudonymisation minimises the risk of sensitive clinical data on an individual patient being intercepted and traced to them. There are no alternative, less intrusive ways to collect the follow up data for this trial. These data will be combined with the baseline data collected by research nurses in a secure environment at the University of Bristol to compare the effectiveness of the two treatments. NHS England data will be required for each patient from their individual trial start date, between 2017-2022, until the end of the study, anticipated 2024.
Only data items necessary for the analysis to derive the primary and secondary outcomes have been requested. Data has been further minimised by requesting only NHS England data for each patient from the date they joined the trial.
Purpose of processing:
HES and Civil Registration data will be processed to derive the primary outcome and secondary outcomes for the trial following a statistical analysis plan which has been developed and will be signed off by the trial management group.
The primary objectives will be to determine the relative effectiveness of high-volume HDF compared with high-flux HD on the first event of non-cancer mortality, hospital admission due to a cardiovascular event or infection (primary outcome).
The secondary objectives are to determine the effect of high-volume HDF on:
• Mortality: from all-causes as well as cause specific
• Morbidity: hospital admissions related to cardiovascular events and infection events
• Quality of life: generic, health utility, disease-specific and time to recover following dialysis
• Indirect effects: laboratory indicators of inflammation, anaemia, bone mineral disorder management
• NHS costs and cost-effectiveness: incremental cost per quality-adjusted life year gained
The joint data controllers are the University of Bristol and North Bristol NHS Trust. The data will be processed at Bristol Randomised Trials Collaboration which is part of the University of Bristol. The Chief Investigator and all co-investigators accessing NHS England data are substantive employees of the University of Bristol.
The lawful basis for processing personal data for the H4RT are Articles 6(1)(e) and 9(2)(j) of the General Data Protection Regulation (2018). These lawful bases can be justified as follows:
Article 6(1)(e), i.e. that the processing is being undertaken as a 'public task': H4RT is an NIHR HTA competitively funded, peer-reviewed randomised controlled trial. It is being Sponsored by an NHS organisation (North Bristol NHS Trust) and delivered by a UK Higher Education Institute (University of Bristol).
Article 9(2)(j), i.e. that the processing is being undertaken in the 'public interest': The need for better evidence on the effectiveness of high-volume HDF to inform NHS care was recognised and prioritised by NIHR (and has subsequently been recognised by NICE). Data is only being processed on participants in the trial, who have all had the research (including the linkage of their trial data with routine healthcare databases) explained to them in an approved patient information sheet by a research nurse with Good Clinical Practice training. All current guidance has been followed to mitigate risk from data processing to participants. There will be no processing of data on members of the public who have not provided consent to take part in the trial.
Both North Bristol NHS Trust and the University of Bristol therefore have a public interest to undertake such processing of personal and sensitive data to advance the evidence base for clinical care and drive improvements in patient survival, hospitalisation and quality of life on dialysis.
The UK Renal Registry will be providing data to the University of Bristol on advanced chronic kidney disease outcomes. Members of the study team, including the chief investigator, were previously part funded by UKRR but employed by NHS. These employees are no longer being funded by UKRR and UKRR is not acting as a data processor.
UK health Security Agency will be asked to provide data to the University of Bristol for infections they collect, such as methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus.
The funder is NIHR Health Technology Assessment. NIHR do not determine the purpose or the manner in which the data will be processed.
Expected output
Study progress and results will be disseminated through the existing communication channels of the UK Renal Registry and the UK Renal Association via newsletters to the renal community. Both have active twitter accounts with more than 3,000 followers. Newsletters and social media accounts at the University of Bristol and North Bristol NHS Trust will additionally be used to disseminate and publicise the study progress and results. An H4RT twitter account has been set up to keep interested patients, carers, clinicians, managers and policy makers up-to-date with trial progress. Representatives from the Kidney Care UK and National Kidney Federation will also use their established channels for communicating the progress and findings of the study to patients such as regular newsletters, active social media accounts, a network of kidney patient associations and annual meetings.
Abstracts for posters and/ or oral presentations will be submitted to national and international conferences, such as UK Kidney Week, ERA-EDTA, American Society of Nephrology and World Congress of Nephrology (estimated 2024).
Peer-reviewed publications will include:
1. Methods paper. Once finalised (estimated Dec 2021), the protocol will be published in an open access academic journal.
2. Main results paper. The primary analysis is expected to occur in Autumn 2025, with the main paper being submitted for publication in Spring 2026. With the key findings likely to be practice changing and of interest to a wide range of clinicians and policy makers, they will be of interest to high impact journals such as the BMJ, the New England Journal of Medicine and the Journal of the American Medical Association. The Bristol Randomised Trials Collaboration has a track record of publishing output from its complex trials in high impact clinical journals and highly respected methodological journals.
Two public and patient involvement (PPI) groups: the Patient Council and local Kidney Patient Association - both comprising 15-20 dialysis and former dialysis/ transplant patients, guided the objectives of this study. Patients wanted to know whether HDF improves survival, symptoms and quality of life, and whether it is safe. Some raised concerns about its environmental impact. A PPI co-applicant helped draft elements of the study protocol. Patients and the public remain active in the running of the trial through the steering committee and patient advisory group. The latter involves annual – biannual meetings where progress and results from the study are presented and patient interpretation sought. Patients in the group then advise on the best way to disseminate the study findings to other patients, including the production of plain English summaries that will be used by patients and carers to assist them in making evidence based treatment decisions and further developing dissemination policy.
The funder (NIHR) requires sight of all output before it is made public (with the exception of individual tweets). The trial management group (chaired by the chief investigator, Fergus Caskey) will determine the dissemination strategy, with approval by the Sponsor (North Bristol NHS Trust) and trials unit (University of Bristol).
Data will only be published in anonymised, aggregate form in line with the HES Analysis Guide.
Benefits reported
The only yielded benefits to date have been the ability of the trial statistician to start working on the first extract of the data to develop the code to clean and analyse the main extract as rapidly as possible in 2025 when follow up finishes and the trial needs to report. The ability to become familiar with the data and write the code will significantly reduce the time to presentation and publication of the main results.
YIELDED BENEFITS UPDATE 2024
There have been no outputs through the processing of the data to date, but there were never intended to be. The data is being processed by the trials statisticians to develop the code that will be used for the main analysis of the second and final extraction of data when the trial follow up is complete (end May 2025.)
DARS-NIC-166879-K4Z0S-v0.19 10 December 2020 to 9 December 2023
- Title
- The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)
- Commercial
- No
- Sublicensing
- No
- Datasets
- 5
- Files released
- 21
Datasets: Civil Registrations of Death - Secondary Care Cut; HES:Civil Registration (Deaths) bridge; Hospital Episode Statistics Admitted Patient Care (HES APC); Hospital Episode Statistics Critical Care (HES Critical Care); Hospital Episode Statistics Outpatients (HES OP)
Objective for processing
End-stage kidney disease (ESKD) affects around 55,000 people in the UK, with around 7,000 newly affected people each year. The survival probability at one, three and five years is around 90, 70 and 50%, respectively. Morbidity is high, with dialysis patients in the UK spending around 15 days in hospital per year. Quality of life on dialysis is also well below that of the general population. There is therefore an unmet and urgent need to improve ESKD patient treatment. Renal replacement therapy (dialysis or transplantation) is necessary when approximately 90% of kidney function is lost. Currently around 90% of existing dialysis patients are on some form of haemodialysis (HD) or haemodiafiltration (HDF). Although HD and HDF can be performed at home, the majority is performed in-centre.
Most people with kidney failure receive blood cleaning treatment (HD) 3 times a week at a hospital or clinic. Adding filtration (the removal and replacement of fluid) to regular HD (which allows toxins to leave the blood with minimal fluid removal/ replacement) results in HDF. As far as the patient is concerned, the two procedures are very similar – they both involve about 4 hours treatment 3 times a week, the dialysis machine is just set up slightly differently. HDF does, however, require a greater volume of high quality water at an increased cost to the NHS and the environment. By removing toxins more effectively, HDF should in theory have benefits, especially if high volumes are used (i.e. more than 21L of water removed and replaced per dialysis session). On the downside, such volumes of filtration could remove essential proteins from the blood stream or introduce toxins or infections from the water supply.
For patients with ESKD who are suitable for kidney transplantation the average waiting time in the UK is 2.8 years. Minimising damage from ESKD during this time is likely to improve their long-term outcomes. For others, kidney transplantation is not an option and quality and quantity of life needs to be optimised. The high-volume HDF vs high-flux HD registry trial (H4RT) is important to patients and the public because existing evidence suggests there may be up to a 40% reduction in mortality if patients receive high-volume HDF. This evidence is weak though, as patients have not previously been randomised to high-volume HDF vs high-flux HD, so the survival advantage may represent the fact that patients who achieve high-volume HDF are fitter. Despite a lack of strong evidence regarding increased patient benefit and cost-effectiveness, around 15% of patients in the UK are currently receiving HDF, with wide centre variation and plans for further adoption. Before this technology diffuses more widely across the UK, a definitive trial is needed to determine whether HDF should be made available to all patients, certain sub-groups of patients, or none.
The H4RT is therefore randomly allocating ESKD patients into either intervention (high-volume HDF) or control (high-flux HD) groups. Patients are 18 or over, and already attending a dialysis unit for maintenance HD or HDF 3 or more times a week in one of 235 possible dialysis units across the UK. Recruitment commenced 1st November 2017 and is ongoing, with funding currently approved until 31st August 2021. All patients have been provided with information about the nature of the trial and how their personal and sensitive data will be processed. Ethical issues have been considered and appropriately addressed, and there are no further issues anticipated. Patients with lack of capacity to consent; predicted life expectancy of less than 3 months; scheduled transition to living kidney donor transplant or home dialysis within 3 months; lack of clinical suitability for HDF; or who started maintenance HD or HDF within 4 weeks are excluded from the trial.
The primary outcome of the trial will be the determination of any difference between high-volume HDF and high-flux HD in terms of non-cancer mortality, and hospital admission due to a cardiovascular event or infection. The secondary outcomes will be the understanding of the impact of high-volume HDF on: cause specific and all causes of mortality; quality of life (generic, health utility, disease-specific and time to recover following dialysis); indirect effects such as inflammation, anaemia and bone mineral disorder management; and NHS costs/ cost-effectiveness (incremental cost per quality adjusted life year).
H4RT was funded on the basis of its "efficient study design", with baseline data collected by research nurses and all follow up being done through (1) linkage with routine healthcare data and (2) centrally administered patient quality of life questionnaires. The move to efficient study designs is in response to a recognition that randomised controlled trials have become very expensive in recent years, making them only affordable when there is a new product being tested with potential to generate profit under a patent. In efficient studies, there are no research visits after the baseline visit, and all subsequent data is collected by mailed/ emailed quality of life questionnaires and linkage to routine healthcare databases.
Data are needed at the individual patient level to follow up each patient in the trial. The University of Bristol will send a cohort including patient identifying information to NHS Digital for linkage, and NHS Digital will return the linked data in a pseudonymised form, providing many of the primary and secondary outcomes for the trial:
• Hospital Episode Statistics – Admitted Patient Care. This is required to derive part of the composite primary outcome, hospital admissions due to cardiovascular and infection events.
• Hospital Episode Statistics – Critical Care. This is required for the heath economics analysis, as admission to intensive care increases hospital admission costs considerably and HDF could influence cardiovascular and infection events that would lead to critical care admission.
• Hospital Episode Statistics – Outpatients. This is required for the health economics analysis, as HDF could influence cardiovascular and infection events that would lead to additional outpatient attendances.
• Civil Registration (Deaths) Secondary Care Cut – This is required to derive the composite primary outcome, non-cancer mortality.
Pseudonymisation minimises the risk of sensitive clinical data on an individual patient being intercepted and traced to them. There are no alternative, less intrusive ways to collect the follow up data for this trial. These data will be combined with the baseline data collected by research nurses in a secure environment at the University of Bristol to compare the effectiveness of the two treatments. NHS Digital data will be required for each patient from their individual trial start date, between 2017-2022, until the end of the study, anticipated 2024.
Only data items necessary for the analysis to derive the primary and secondary outcomes have been requested. Data has been further minimised by requesting only NHS Digital data for each patient from the date they joined the trial.
Purpose of processing:
HES and Civil Registration data will be processed to derive the primary outcome and secondary outcomes for the trial following a statistical analysis plan which has been developed and will be signed off by the trial management group.
The primary objectives will be to determine the relative effectiveness of high-volume HDF compared with high-flux HD on the first event of non-cancer mortality, hospital admission due to a cardiovascular event or infection (primary outcome).
The secondary objectives are to determine the effect of high-volume HDF on:
• Mortality: from all-causes as well as cause specific
• Morbidity: hospital admissions related to cardiovascular events and infection events
• Quality of life: generic, health utility, disease-specific and time to recover following dialysis
• Indirect effects: laboratory indicators of inflammation, anaemia, bone mineral disorder management
• NHS costs and cost-effectiveness: incremental cost per quality-adjusted life year gained
The joint data controllers are the University of Bristol and North Bristol NHS Trust. The data will be processed at Bristol Randomised Trials Collaboration which is part of the University of Bristol. The Chief Investigator and all co-investigators accessing NHS Digital data are substantive employees of the University of Bristol.
The lawful basis for processing personal data for the H4RT are Articles 6(1)(e) and 9(2)(j) of the General Data Protection Regulation (2018). These lawful bases can be justified as follows:
Article 6(1)(e), i.e. that the processing is being undertaken as a 'public task': H4RT is an NIHR HTA competitively funded, peer-reviewed randomised controlled trial. It is being Sponsored by an NHS organisation (North Bristol NHS Trust) and delivered by a UK Higher Education Institute (University of Bristol).
Article 9(2)(j), i.e. that the processing is being undertaken in the 'public interest': The need for better evidence on the effectiveness of high-volume HDF to inform NHS care was recognised and prioritised by NIHR (and has subsequently been recognised by NICE). Data is only being processed on participants in the trial, who have all had the research (including the linkage of their trial data with routine healthcare databases) explained to them in an approved patient information sheet by a research nurse with Good Clinical Practice training. All current guidance has been followed to mitigate risk from data processing to participants. There will be no processing of data on members of the public who have not provided consent to take part in the trial.
Both North Bristol NHS Trust and the University of Bristol therefore have a public interest to undertake such processing of personal and sensitive data to advance the evidence base for clinical care and drive improvements in patient survival, hospitalisation and quality of life on dialysis.
The UK Renal Registry will be providing data to the University of Bristol on advanced chronic kidney disease outcomes. Members of the study team, including the chief investigator, were previously part funded by UKRR but employed by NHS. These employees are no longer being funded by UKRR and UKRR is not acting as a data processor.
Public Health England will be asked to provide data to the University of Bristol for infections they collect, such as methicillin-resistant Staphylococcus aureus and methicillin-susceptible Staphylococcus aureus.
The funder is NIHR Health Technology Assessment. NIHR do not determine the purpose or the manner in which the data will be processed.
Expected output
Study progress and results will be disseminated through the existing communication channels of the UK Renal Registry and the UK Renal Association via newsletters to the renal community. Both have active twitter accounts with more than 3,000 followers. Newsletters and social media accounts at the University of Bristol and North Bristol NHS Trust will additionally be used to disseminate and publicise the study progress and results. An H4RT twitter account has been set up to keep interested patients, carers, clinicians, managers and policy makers up-to-date with trial progress. Representatives from the Kidney Care UK and National Kidney Federation will also use their established channels for communicating the progress and findings of the study to patients such as regular newsletters, active social media accounts, a network of kidney patient associations and annual meetings.
Abstracts for posters and/ or oral presentations will be submitted to national and international conferences, such as UK Kidney Week, ERA-EDTA, American Society of Nephrology and World Congress of Nephrology (estimated 2024).
Peer-reviewed publications will include:
1. Methods paper. Once finalised (estimated Dec 2021), the protocol will be published in an open access academic journal.
2. Main results paper. The primary analysis is expected to occur in Spring 2024, with the main paper being submitted for publication in Summer 2024. With the key findings likely to be practice changing and of interest to a wide range of clinicians and policy makers, they will be of interest to high impact journals such as the BMJ, the New England Journal of Medicine and the Journal of the American Medical Association. The Bristol Randomised Trials Collaboration has a track record of publishing output from its complex trials in high impact clinical journals and highly respected methodological journals.
Two public and patient involvement (PPI) groups: the Patient Council and local Kidney Patient Association - both comprising 15-20 dialysis and former dialysis/ transplant patients, guided the objectives of this study. Patients wanted to know whether HDF improves survival, symptoms and quality of life, and whether it is safe. Some raised concerns about its environmental impact. A PPI co-applicant helped draft elements of the study protocol. Patients and the public remain active in the running of the trial through the steering committee and patient advisory group. The latter involves annual – biannual meetings where progress and results from the study are presented and patient interpretation sought. Patients in the group then advise on the best way to disseminate the study findings to other patients, including the production of plain English summaries that will be used by patients and carers to assist them in making evidence based treatment decisions and further developing dissemination policy.
The funder (NIHR) requires sight of all output before it is made public (with the exception of individual tweets). The trial management group (chaired by the chief investigator, Fergus Caskey) will determine the dissemination strategy, with approval by the Sponsor (North Bristol NHS Trust) and trials unit (University of Bristol).
Data will only be published in anonymised, aggregate form in line with the HES Analysis Guide.
Benefits reported
Yielded Benefits is not a requirement for new applications.
Register history
When this agreement appeared in, or was edited in, each monthly edition of the register. Built by comparing every edition this site holds, the earliest of which is July 2021.
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July 2021 —
already listed in the earliest edition this site holds, so it may be older. 1 version: DARS-NIC-166879-K4Z0S-v0.19
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April 2024
1 version added: DARS-NIC-166879-K4Z0S-v1.6
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August 2025
1 version added: DARS-NIC-166879-K4Z0S-v2.2
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February 2026
1 version added: DARS-NIC-166879-K4Z0S-v3.3
Cite this page
NHS England (2026) Data Uses Register, September 2026 edition, agreement DARS-NIC-166879-K4Z0S, “The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)”. Read via NHS Data Access Explorer (unofficial), https://healthdatauses.uk/agreements/dars-nic-166879-k4z0s/ (accessed [date]).
This address stays the same, but the page is rebuilt with each monthly edition, so the citation names the edition it shows. Every edition's data is kept in the facts store.
Source: datausesregister_september2026.xlsx, September 2026 edition of the NHS England Data Uses Register. Search that workbook for DARS-NIC-166879-K4Z0S to see the original rows.