A study comparing a form of haemodialysis that filters and replaces high volumes of blood water during each treatment (high-volume haemodiafiltration) with a form of haemodialysis that doesn’t (high-flux haemodialysis)

Plain English Summary

Background and study aims
Most people with kidney failure need blood cleaning treatment (haemodialysis) for four hours three times a week up at a hospital/clinic. This is for the rest of their life unless they are fit to receive a kidney transplant. Survival and quality of life on haemodialysis are poor. The addition of filtration (the removal and replacement of fluid) to regular haemodialysis (which allows toxins to leave the blood with minimal fluid removal/ replacement) is known as haemodiafiltration. The aim of this study is to see whether removing and replacing 21 or more litres of fluid from the blood at the time of a standard dialysis treatment reduces death or hospitalisation from cardiac events or infections in people with kidney failure. Effects on quality of life, admission to hospital, symptoms, infection rates and costs are also examined.

Who can participate?
Adults aged 18 and older who are receiving dialysis treatments three times a week.

What does the study involve?
This study will randomly allocate patients already on dialysis in one of 20 centres in the UK are randomly allocated to switch to either haemodialysis or haemodiafiltration. This does not noticeably change the dialysis procedure as far as the patient is concerned – it is still 4 hours 3 times a week – it just requires changes in equipment and nurse practice. It does however require a greater volume of high-quality water. A research nurse collects the initial clinical information. All follow-up is carried out using data already routinely collected by the UK Renal Registry or by linking with other health care databases. Quality of life information is collected. Interviews are carried out and conversations studied in the preparatory and recruitment stages of the study.

What are the possible benefits and risks of participating?
Participants may benefit haemodiafiltration may improve survival as it may remove toxins more effectively, especially if high volumes are used (i.e. more than 21L of water removed and replaced per session. On the downside, such volumes of filtration could remove essential proteins or introduce toxins or infections from the water supply. Therefore it is needed to establish if haemodiafiltration results in benefits to patients, is safe and justifies any additional financial and environmental (e.g. water) costs.

Where is the study run from?
This study is being run by the University of Bristol (UK) and takes place in different hospitals in the UK.

When is the study starting and how long is it expected to run for?
May 2017 to September 2025 (updated 20/08/2021, previously: March 2024)

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
1. Dr Sunita Procter
H4rt-study@bristol.ac.uk
2. Prof Fergus Caskey
Fergus.caskey@bristol.ac.uk

Study website

http://www.bristol.ac.uk/population-health-sciences/projects/h4rt-trial/

Type

Public

Contact name

Dr Sunita Procter

ORCID ID

http://orcid.org/0000-0002-2174-600X

Contact details

Population Health Sciences
Bristol Medical School
University of Bristol
Canynge Hall
39 Whatley Road
Bristol
BS8 2PS
United Kingdom
+44 (0)117 928 7286
H4rt-study@bristol.ac.uk

Type

Scientific

Contact name

Prof Fergus Caskey

ORCID ID

http://orcid.org/0000-0002-5199-3925

Contact details

Learning and Research
Southmead Hospital
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
+44 (0)117 414 8150
Fergus.caskey@bristol.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

227067

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 34704, IRAS 226067

Scientific title

The High-volume Haemodiafiltration vs High-flux Haemodialysis Registry Trial (H4RT)

Acronym

H4RT

Study hypothesis

The aim is to establish the effectiveness and cost-effectiveness of high-volume HDF compared with high-flux HD in adult patients with ESKD on maintenance thrice weekly in-centre HD. This will be done by running a randomised controlled trial using non-cancer mortality or hospital admission due to a cardiovascular event or infection as our primary outcome.

Ethics approval(s)

South Central – Berkshire Research Ethics Committee, 07/09/2017, ref: 17/SC/0391

Study design

Randomized; Interventional; Design type: Treatment, Device, Complex Intervention

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Renal failure

Intervention

Participants in the intervention arm receive in-centre, high-volume, post-dilution HDF typically for four hours, three times a week. Participants in the control arm receive in-centre high-flux HD typically for four hours, three times a week.

Participants in both arms are followed up for 32 months minimum (50 months maximum) using six monthly paper or electronic questionnaires. Follow up data are also accessed by linking to routine healthcare databases i.e. UK Renal Registry, Hospital Episode Statistics and Office for National Statistics data (and their equivalents in Wales, Scotland and Northern Ireland).

Intervention type

Device

Pharmaceutical study type(s)

Phase

Not Applicable

Drug/device/biological/vaccine name(s)

Not provided at time of registration

Primary outcome measure

1. Non-cancer mortality or hospital admission with a cardiovascular event or infection from randomisation to end of follow-up
2. A composite of first of non-cancer mortality or admission to hospital related to a cardiovascular event or infection is measured using datasets (UKRR, Hospital Statistics & ONS) from randomisation to end of follow-up (32-50 months depending on recruitment)

Secondary outcome measures

1. All-cause mortality, cardiovascular and infection related morbidity and mortality. Health-related quality of life (QoL), cost effectiveness and environmental impact
2. All-cause mortality is measured using datasets (UKRR and ONS) from randomisation to end of follow-up (32-50 months depending on recruitment)
3. Cardiovascular – cause specific hospitalisation and mortality is measured using datasets ((UKRR, Hospital Statistics (HES, PEDW, ISD, NISRA) & ONS) from randomisation to end of follow-up (32-50 months depending on recruitment)
4. Infection – cause- specific hospitalisation and mortality using datasets (MRSA & MSSA) (Public Health England) from randomisation to end of follow-up (32-50 months depending on recruitment)
5. Health-related quality of life (QoL) – quality adjusted life years gained (EQ-5D-5L), generic quality of life (SF-36), disease specific (kidney symptoms within KDQOL-36) and time to recover after dialysis: From Patient Questionnaires - assessed using repeated measures taken six-monthly
6. Cost effectiveness and environmental impact (including locally purified water, manufactured saline and plastic consumables): using all available data for the full duration of follow-up (32-50 months)

Overall study start date

01/05/2017

Overall study end date

30/09/2025

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Adult patients aged 18 and older receiving in-centre, maintenance HD or HDF for ESKD
2. Dialysing three times a week in a main dialysis unit or satellite unit
3. Potential to achieve high-volume HDF

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

Planned Sample Size: 1550; UK Sample Size: 1550

Total final enrolment

1553

Participant exclusion criteria

1. Lack of capacity to consent
2. Clinician predicted prognosis of less than 3 months
3. Started maintenance HD within the preceding 4 weeks
4. Transition to living kidney donor transplant or home dialysis scheduled within next 3 months
5. Not suitable for high-volume HDF for other clinical reasons such as dialysis less than thrice weekly or unlikely to achieve sufficient blood flow rates with current vascular access
6. Treatment with HDF for more than 3 months prior to inclusion in the trial or prior intolerance of HDF

Recruitment start date

01/11/2017

Recruitment end date

08/09/2022

Countries of recruitment

England, Scotland, United Kingdom

Study participating centre

Southmead Hospital
North Bristol NHS Trust (Lead Centre)
Southmead Road
Westbury-On-Trym
Bristol
BS10 5NB
United Kingdom

Study participating centre

Queens Medical Centre
Nottingham University Hospitals NHS Trust
Trust Headquarters
Derby Road
Nottinghamshire
Nottingham
NG7 2UH
United Kingdom

Study participating centre

Ipswich Hospital NHS Trust
Heath Road
Ipswich Suffolk
Ipswich
IP4 5PD
United Kingdom

Study participating centre

Salford Royal Hospital
Salford Royal NHS Foundation Trust
Stott Lane
Salford Greater Manchester
Salford
M6 8HD
United Kingdom

Study participating centre

Freeman Hospital
The Newcastle-Upon-Tyne Hospitals NHS Foundation Trust
Freeman Road
High Heaton
Newcastle-Upon-Tyne
NE7 7DN
United Kingdom

Study participating centre

Edinburgh Royal Infirmary Renal Department
51 Little France Drive
Edinburgh
EH16 4SA
United Kingdom

Study participating centre

Bradford Royal Infirmary
Bradford Teaching Hospitals NHS Foundation Trust
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Study participating centre

University Hospitals Of North Midlands NHS Trust
Newcastle Road
Staffordshire
Stoke-On-Trent
ST4 6QG
United Kingdom

Study participating centre

Aberdeen Royal Infirmary Renal Unit
Foresterhill
Aberdeen
AB25 2ZN
United Kingdom

Study participating centre

Queen Elizabeth University Hospital Renal Unit
1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Study participating centre

The Royal London Hospital
London
E1 1BB
United Kingdom

Study participating centre

Royal Free Hospital
London
NW3 2QG
United Kingdom

Study participating centre

Nottingham University Hospitals NHS Trust - City Campus
Nottingham
NG5 1PB
United Kingdom

Study participating centre

University Hospital Coventry
Coventry
CV2 2DX
United Kingdom

Study participating centre

Lister Hospital
Stevenage
SG1 4AB
United Kingdom

Study participating centre

St Luke's Hospital
Bradford
BD5 0NA
United Kingdom

Study participating centre

Royal Cornwall Hospital (Treliske)
Truro
TR1 3LQ
United Kingdom

Study participating centre

Manchester Royal Infirmary
Manchester
M13 9WL
United Kingdom

Study participating centre

Kent & Canterbury Hospital
Canterbury
CT1 3NG
United Kingdom

Study participating centre

Guy's and St Thomas' NHS Foundation Trust
London
SE1 9RT
United Kingdom

Study participating centre

Leicester General Hospital
Leicester
LE5 4PW
United Kingdom

Study participating centre

Derriford Hospital
Plymouth
PL6 8DH
United Kingdom

Study participating centre

City Hospitals Sunderland
Sunderland
SR4 7TP
United Kingdom

Study participating centre

Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Study participating centre

Victoria Hospital
Kirkcaldy
KY2 5AH
United Kingdom

Study participating centre

The James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom

Study participating centre

Sheffield Teaching Hospitals
Sheffield
S5 7AU
United Kingdom

Study participating centre

Queen Alexandra Hospital
Portsmouth
PO6 3LY
United Kingdom

Study participating centre

Royal Liverpool and Broadgreen University Hospital
Liverpool
L7 8XP
United Kingdom

Study participating centre

Colchester General Hospital
Colchester
CO4 5JL
United Kingdom

Study participating centre

Oxford University Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Study participating centre

Epsom and St Helier University Hospital
Dorking Road
Epsom
KT18 7EG
United Kingdom

Study participating centre

St George's University Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Study participating centre

Worthing Hospital
University Hospitals Sussex NHS Foundation
Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

Organisation

North Bristol NHS Trust

Sponsor details

Southmead Hospital
Southmead Road
Westbury-On-Trym
Bristol
BS10 5NB
England
United Kingdom

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/036x6gt55

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

Academic publications will be targeted at high impact general medical journals such as the BMJ, the New England Journal of Medicine and the Journal of the American Medical Association. Findings will be presented at leading nephrology conferences in Europe (the ERA-EDTA Annual Congress) and North America (The American Society of Nephrology Kidney Week) as well as at the UK Kidney Week, co-hosted by the Renal Association and the multi-disciplinary British Renal Society. Findings will also be used to inform future iterations of the NICE-approved UK Renal Association clinical guidelines and the European Renal Best Practice clinical guidelines.

The H4RT protocol is available at reference URL: https://www.journalslibrary.nihr.ac.uk/programmes/hta/158052/#/
A statistical analysis plan approved by the trial steering committee will be made publicly available in due course.

Intention to publish date

30/09/2025

Individual participant data (IPD) sharing plan

The data sharing plans for the current study are unknown and will be made available at a later date

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs