title: Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial.
abstract: BACKGROUND
  Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD.
  
  
  METHODS
  The STOP-ACEi trial (trial registration: current controlled trials, ISRCTN62869767) is an investigator-led multicentre open-label, randomized controlled clinical trial of 410 participants with advanced (Stage 4 or 5) progressive CKD receiving ACEi, ARBs or both. Patients will be randomized in a 1:1 ratio to either discontinue ACEi, ARB or combination of both (experimental arm) or continue ACEi, ARB or combination of both (control arm). Patients will be followed up at 3 monthly intervals for 3 years. The primary outcome measure is eGFR at 3 years. Secondary outcome measures include the number of renal events, participant quality of life and physical functioning, hospitalization rates, BP and laboratory measures, including serum cystatin-C. Safety will be assessed to ensure that withdrawal of these treatments does not cause excess harm or increase mortality or cardiovascular events such as heart failure, myocardial infarction or stroke.
  
  
  RESULTS
  The rationale and trial design are presented here. The results of this trial will show whether discontinuation of ACEi/ARBs can improve or stabilize renal function in patients with advanced progressive CKD. It will show whether this simple intervention can improve laboratory and clinical outcomes, including progression to end-stage renal disease, without causing an increase in cardiovascular events.
authors.affiliation: Department of Renal Medicine, Hull and East Yorkshire Hospitals NHS Trust, Kingston upon Hull, UK Hull York Medical School, East Yorkshire, UK.
authors.forename: Sunil
authors.initials: S
authors.lastname: Bhandari
authors.affiliation: Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ives
authors.affiliation: Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Brettell
authors.affiliation: Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Valente
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.affiliation: Department of Renal Medicine, Leicester General Hospital, Leicester, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Topham
authors.affiliation: National Heart & Lung Institute, Imperial College London, London, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Sheffield Kidney Institute, Sheffield, UK.
authors.forename: Arif
authors.initials: A
authors.lastname: Khwaja
authors.affiliation: Sheffield Kidney Institute, Sheffield, UK.
authors.forename: Meguid
authors.initials: M
authors.lastname: El Nahas
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D028761:Withholding Treatment
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: angiotensin II receptor blocker (ARB); angiotensin-converting enzyme inhibitor (ACEi); chronic kidney disease; eGFR; randomized controlled trial