Impact of renin-angiotensin system inhibitors continuation versus discontinuation on outcome after major surgery: protocol of a multicenter randomized, controlled trial (STOP-or-NOT trial)

Trials. 2019 Mar 5;20(1):160. doi: 10.1186/s13063-019-3247-1.

Abstract

Background: Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery.

Methods: This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%.

Discussion: The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery.

Trial registration: ClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017.

Keywords: ACE inhibitors; ARB; Acute kidney injury; Complications; Mortality; Outcome; Strategy; Surgery.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Angiotensin Receptor Antagonists / administration & dosage*
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Drug Administration Schedule
  • France
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Multicenter Studies as Topic
  • Perioperative Care / adverse effects
  • Perioperative Care / methods*
  • Postoperative Complications / etiology
  • Randomized Controlled Trials as Topic
  • Renin-Angiotensin System / drug effects*
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03374449