Angiotensin converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) withdrawal in advanced renal disease

Not Applicable

Completed

• Conditions: Topic: Renal and Urogenital; Subtopic: Renal and Urogenital (all Subtopics); Disease: Renal; Urological and Genital Diseases

• Registration Number: ISRCTN62869767
• Lead Sponsor: Hull University Teaching Hospitals NHS Trust

Brief Summary

2016 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/26429974 protocol 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36326117/ (added 07/12/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-25
• Study Completion: 2021-12-31
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 411

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
<br> 1. Cystatin-C<br> 2. Blood pressure<br> 3. Number of participants starting renal replacement therapy or sustaining a >50% decline in eGFR<br> 4. Time taken to reach ESRD or need for renal replacement therapy<br> 5. Hospitalisation rates from any cause<br> 6. Participant quality of life and wellbeing (measured using the KDQOL-SF™ v1.3 questionnaire)<br> 7. Participant physical function (measured using the 6-minute walk test)<br> 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<br> 9. Mortality<br> 10. Urine protein excretion<br> 11. Haemoglobin concentration<br> 12. Dose of ESA<br>