Condition category
Urological and Genital Diseases
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Chronic kidney disease (CKD) affects 1 in 10 adults in the UK and describes progressive loss of kidney function regardless of the original kidney disease. CKD can have serious effects for those affected, including a risk of CKD progressing to complete kidney failure so that replacement of kidney function by dialysis or transplantation is required. Kidney disease is expensive with a high proportion of the health-care budget spent on CKD; the cost of dialysis alone is about £30,000 per year. Patient quality of life can be poor, with dialysis leading to early death. Treating high blood pressure (BP) is the most important intervention that can slow CKD progression. Some people with CKD gain additional protection from a type of drug, Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs). These drugs treat high BP but also slow CKD progression by other means. However, recent research suggests that in some people with advanced CKD (stages 4 & 5) who are progressing to complete kidney failure and are receiving treatment with an ACEi and/or ARB, stopping these drugs leads to stabilisation and improvement of kidney function and decreases or delays the need for dialysis. This indicates that in some patients the very tablets used to protect the kidneys may be contributing to a harmful decline in their function by some currently unknown mechanism. To date, research on this is observational and a study to confirm the association between stopping these drugs and stabilisation of kidney function is required. In this study we will randomly allocate suitable participants to either continue or stop their ACEi/ARB treatment and follow-up participants for 3 years. This study is needed before this treatment strategy can be put into routine clinical practice. In addition, we will look at the other effects of stopping these drugs such as cardiovascular effects and participant quality of life.

Who can participate?
Men and women, aged 18 years and older, diagnosed with chronic kidney disease.

What does the study involve?
Participants will be randomly allocated to either continue or discontinue their ACEi and/or ARB treatment.

What are the possible benefits and risks of participating?
Participants in research studies such as this receive very close monitoring, which will be advantageous to their general health. Although participants may not receive any individual benefit from taking part in the study, the information we get from the study may help us to improve the treatment of all people in the UK with stage 4 or 5 CKD in the future. It is not currently known whether treating people with advanced CKD with ACEi and/or ARBs is beneficial or not. For participants that are allocated to continue with their current ACEi and/or ARB treatment, there will be no additional risk in the study than would normally be encountered in routine clinical care, but if the assumption of this study is correct, there is the risk that the participant’s CKD may get worse by staying on ACEi and/or ARBs. For participants that are allocated to the discontinuation group, there is the risk that stopping their existing ACEi and/or ARB treatment will cause a loss of the protective effect of ACEi and/or ARBs and an increase in blood pressure. To counteract the loss of antihypertensive therapy (drugs to lower blood pressure), participants that stop their ACEi and/or ARBs will start alternative antihypertensive drugs (e.g. calcium channel blockers, diuretics etc). However, we recognise that drug withdrawal requires close monitoring and the potential risk of increased cardiovascular events for participants will be carefully assessed throughout the study by the Date Monitoring and Ethics Committee. If the results of the study show a benefit for ACEi/ARB withdrawal, it could have a huge impact on patients, their families and health services, by reducing or delaying the need for dialysis and kidney transplantation. We have worked to minimise risk by ensuring that patients are closely monitored and that blood pressure is controlled by alternative means throughout the study. If the treating clinician feels that ACEi/ARB is required, this will be permitted. In patients with advanced CKD there are theoretical reasons why ACEi/ARB may be useful, useless or harmful. In practice, some clinicians withdraw these agents in patients with advanced CKD but others do not. It is important for care of patients that controversy and debate evolves into evidence-based guidelines.

Where is the study run from?
The study will be run at about 20 sites in Britain. For an up-to-date list of hospitals taking part in the study, please see the study website

When is the study starting and how long is it expected to run for?
April 2014 to April 2016

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

Who is the main contact?

Trial website

Contact information



Primary contact

Miss Marie Valente


Contact details

Birmingham Clinical Trials Unit
University of Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2013-003798-82 number

Protocol/serial number

15908; EME 11/30/07

Study information

Scientific title

Multi-centre randomised controlled trial of angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) withdrawal in advanced renal disease: the STOP-ACEi trial



Study hypothesis

That stopping ACEi or ARB treatment, or a combination of both, compared with continuing on these treatments, improves or stabilises renal function in patients with progressive stage 4 or 5 CKD based on assessment of renal function using the Modification of Diet in Renal Disease (MDRD) 4-variable estimated Glomerular Filtration Rate (eGFR) at 3 years follow-up.

More details can be found at:
Protocol can be found at:

Ethics approval

Yorkshire and The Humber (Leeds East) Research Ethics Committee, 29/01/2014, ref: 13/YH/0394

Study design

Randomised; Interventional; Design type:Treatment

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet

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


Topic: Renal and Urogenital; Subtopic: Renal and Urogenital (all Subtopics); Disease: Renal


Participants will be randomly allocated to either continue or discontinue their ACEi and/or ARB treatment.

Continue ACEi/ARB arm: participants will continue with their current, standard treatment with ACEi and/or ARBs. The choice and dose of ACEi/ARB will be at the treating clinician’s discretion.
Discontinue ACEi/ARB arm: participants will stop their existing ACEi and/or ARB treatment and will be started on alternative standard antihypertensives to ensure continued blood pressure control. The choice and dose of antihypertensives will be at the treating clinician’s discretion.

Follow Up Length: 36 month(s)
Study Entry : Single Randomisation only

Intervention type



Not Applicable

Drug names

Primary outcome measures

Renal function measured using MDRD 4-variable eGFR at 3 years

Secondary outcome measures

1. Cystatin-C
2. Blood pressure
3. Number of participants starting renal replacement therapy or sustaining a >50% decline in eGFR
4. Time taken to reach ESRD or need for renal replacement therapy
5. Hospitalisation rates from any cause
6. Participant quality of life and wellbeing (measured using the KDQOL-SF™ v1.3 questionnaire)
7. Participant physical function (measured using the 6-minute walk test)
8. That withdrawal of these treatments does not cause excess harm (e.g. increased cardiovascular events such as heart failure, hypertension, myocardial infarction, stroke) and is not associated with an increase in adverse effects
9. Mortality
10. Urine protein excretion
11. Haemoglobin concentration
12. Dose of ESA

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Aged ≥18 years (male or female)
2. CKD stage 4 or 5 (eGFR <30 ml/minute using the MDRD equation) and not on dialysis therapy
3. Progressive deterioration in renal function (fall in eGFR of >2 ml/min/year over previous 12-24 months) as measured by linear regression analysis. A simple excel spreadsheet for calculation of this will be provided to all sites. A minimum of 3 measurements of eGFR over the previous 12-24 months are required to identify a >2 ml/min/year fall. The last eGFR must be within 3 months of randomisation
4. Treatment with either an ACEi or ARB, or a combination of both, for >6 months with at least 25% of the maximum recommended daily dose on the day of consent
5. Resting blood pressure (BP) ≤160/90 mmHg when measured in accordance with British Hypertension Society guidelines in clinic or home blood pressure readings within the previous month or a 24 h ambulatory blood pressure measurement within the last 3 months are acceptable
6. At least 3 months of specialist renal follow-up at the time of entry into the trial
7. Written, signed informed consent to the trial

Participant type


Age group




Target number of participants

Planned Sample Size: 410; UK Sample Size: 410

Participant exclusion criteria

1. Aged <18 years
2. Uncontrolled hypertension (>160/90 mmHg) or requirement for 5 or more agents to control BP
3. Undergoing dialysis therapy
4. Any condition which, in the opinion of the investigator, makes the participant unsuitable for trial entry due to prognosis/terminal illness with a projected survival of less than 12 months
5. History of myocardial infarction or stroke in preceding 3 months
6. Participation in an interventional research study in preceding 6 weeks
7. Pregnancy, confirmed by positive pregnancy test, or breastfeeding
8. Inability to provide informed consent (e.g. due to cognitive impairment)
9. Immune-mediated renal disease requiring disease-specific treatment
10. Known drug or alcohol abuse
11. Inability to comply with the trial schedule and follow-up

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
B15 2TT
United Kingdom

Sponsor information


Hull and East Yorkshire Hospitals NHS Trust (UK)

Sponsor details

Research & Development Department
2nd Floor Daisy Building
Castle Hill Hospital
HU16 5JQ
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Efficacy and Mechanism Evaluation Programme

Alternative name(s)

NIHR Efficacy and Mechanism Evaluation programme, EME

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date


Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 protocol in:

Publication citations

Additional files

Editorial Notes

20/10/2016: Publication reference added.