Progressive, advanced (stage 4 or 5) chronic kidney disease (CKD). NB. There was not an appropriate therapeutic area in the drop down menu in E1-1. Have selected 'Male diseases of the urinary and reproductive systems', but this trial is for a disease of the male and female urinary system. MedDRA version: 20.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100
Conditions
Interventions
Trade Name: Candesartan
Product Name: Angiotensin Receptor Blocker (ARB)
Pharmaceutical Form: Tablet
Product Name: Angiotensin Converting Enzyme Inhibi
Sponsors
Hull & East Yorkshire Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Aged =18 years (male or female); •CKD stages 4 or 5 (eGFR 2ml/min/year over previous 12-24 months) as measured by linear regression analysis. A simple excel spread sheet 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 >2ml/min fall. Last eGFR must be within three months of randomisation. •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; •Resting blood pressure (BP) =160/90 mmHg when measured in accordance with British Hypertension Society guidelines in clinic or recent home blood pressure readings within the previous month or a 24h ambulatory blood pressure measurement within in the last 3 months are acceptable. •At least 3 months of specialist renal follow-up at the time of entry into the trial; •Written, signed informed consent to the trial. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 226 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 185
Exclusion criteria
Exclusion criteria: •Aged 160/90mmHg) or requirement for 5 or more agents to control BP; •Undergoing dialysis therapy; •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; •History of myocardial infarction or stroke in preceding 3 months; •Participation in an interventional research study in preceding 6 weeks; •Pregnancy, confirmed by positive pregnancy test or breastfeeding; •Inability to provide informed consent (e.g. due to cognitive impairment); •Immune mediated renal disease requiring disease specific treatment; •Known drug or alcohol abuse; •Inability to comply with the trial schedule and follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Renal function measured using MDRD 4-variable eGFR over 3 years.;Main Objective: To test the 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 stages 4 or 5 chronic kidney disease (CKD) based on assessment of renal function using the Modification of Diet in Renal Disease (MDRD) 4-variable estimated Glomerular Filtration Rate (eGFR) over 3 years follow-up.; Secondary Objective: To test whether in each of the randomised groups: Clinical outcomes •Cystatin-C levels differ; •Blood pressure control is the same; •The number of participants starting renal replacement therapy or sustaining a >50% decline in eGFR differs; •There is a difference in the time taken to reach ESRD or need for renal replacement therapy; •Hospitalisation rates from any cause are different; •Participant quality of life and wellbeing (measured using the KDQOL-SF™ v1.3 questionnaire) differs; •Participant physical function (measured using the 6-minute walk test) differs; •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; •Participant survival in each group is similar; Mechanistic Outcomes •There is a change in urine protein excretion; •Discontinuation of ACEi/ARB affects haemoglobin concentration; •Discontinuation of ; Timepoint(s) of evaluation of this end point: The primary outcome is the continuous measure eGFR at 3 years. These data will be summarised using means and standard deviations, with differences | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Other laboratory measures of renal function including serum creatinine and cystatin C •Blood pressure •Renal events such as ESRD and the need to start renal replacement therapy (dialysis) •Time taken to reach ESRD or requirement for renal replacement therapy •Hospitalisation from any cause •Participant QOL (using the KDQOL-SF™ v1.3 questionnaire) •Physical function using the 6-minute walk test •Cardiovascular events such as stroke and myocardial infarction •Adverse events •All-cause mortality •Urine protein excretion (e.g. ACR or PCR) •Hb concentration •Dose of ESA ;Timepoint(s) of evaluation of this end point: Participants will be assessed every 3 months for 3 years and details relating to the secondary end points will be documented at each of these time points. Time-to-event measures will be evaluated as they occur. | — |
Countries
United Kingdom
Contacts
Public ContactSTOP-ACEi Trial Manager
Birmingham Clinical Trials Unit
Outcome results
None listed