Kidney Week

Abstract: TH-PO966

Multi-Center Randomized Controlled Trial of Angiotensin Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) Withdrawal in Advanced Kidney Disease: The STOP-ACEi Trial

Session Information

• Late-Breaking Clinical Trials (Posters)
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

• Bhandari, Sunil, Hull University Teaching Hospitals NHS Trust, Hull, Kingston upon Hull, United Kingdom

Sunil Bhandari,

• Khwaja, Arif, Northern General Hospital Sheffield Kidney Institute, Sheffield, South Yorkshire, United Kingdom

Arif Khwaja,

• Ives, Natalie, University of Birmingham, Birmingham, Birmingham, United Kingdom

Natalie Ives,

• Cleland, John G.F., University of Glasgow, Glasgow, Glasgow, United Kingdom

John G.F. Cleland,

• Cockwell, Paul, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

Paul Cockwell,

• Mehta, Samir, University of Birmingham, Birmingham, Birmingham, United Kingdom

Samir Mehta,

• Brettell, Elizabeth Ann, University of Birmingham, Birmingham, Birmingham, United Kingdom

Elizabeth Ann Brettell,

• Chadburn, Marie, University of Birmingham, Birmingham, Birmingham, United Kingdom

Marie Chadburn,

Group or Team Name

• STOP ACEi Investigators and Committees

Background

Angiotensin Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) slow progression of mild to moderate chronic kidney disease (CKD). However small studies have reported delayed progression in patients with advanced CKD after discontinuation of ACEi/ARBs. We assessed whether discontinuation of ACEi/ARBs could slow progression of CKD in patients with advanced CKD in the STOP-ACEi Trial (methods paper-NDT 2016; 31(2):255-61)

Methods

In this open label, phase 2, multicenter, randomized controlled trial, we recruited adult patients with stage 4-5 CKD receiving ACEi and/or ARB from 37 UK renal centers. Patients were randomlized (1:1 ratio) to discontinue (experimental arm) or continue (control arm) ACEi/ARB. Patients were stratified based on age, baseline eGFR, diabetes, BP and proteinuria.

Outcomes were assessed in an intention to treat population. The primary endpoint is kidney function (MDRD 4-variable eGFR) at 3y between the two groups and will be analyzsed using a linear regression model. Sensitivity analysis will be undertaken including use of pattern mixture and joint models.

Secondary outcome measures include the number starting renal replacement therapy (RRT) and/or sustaining a >50% decline in eGFR, quality of life/wellbeing, hospitalization rates, and safety measures including cardiovascular event rates and mortality.

Results

Between 11 July 2014-19 June 2018 we recruited 411 patients (target 410), 206 to the discontinuation and 205 to the continuation arm. Median age was 63.4y (interquartile range: 51.5-72.1) and 31.6% were women; 85.4% white, 7.2% Asian and 5.6% black. In total 37.3% were diabetic (32.4% type II diabetes).

Median baseline creatinine was 299 (243-367)µmol/L, eGFR was 18 (14-22)mL/min/1.73m²; urinary protein:creatinine ratio was 115mg/mmol (28-248). Comorbidities: 71% with hypertension; 14% ischemic heart disease; 45% atrial fibrillation; 5% peripheral vascular disease, 4% with heart failure and 6% with a previous history of stroke. We will present the primary and key secondary outcomes, including progression to RRT, cardiovascular events and death.

Conclusion

The results of this trial will inform future clinical practice worldwide and guideline recommendations.

Funding

• Government Support - Non-U.S.