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)

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.

Conflict of interest statement

Authors’ information

Correspondence should be addressed to Matthieu Legrand.

Ethics approval and consent to participate

Included in the manuscript.

Consent for publication

Not applicable.

Competing interests

ML reports consulting fees from Novartis, lecture fees from Baxter and Freseniu, Research support from Shingotec. EF received consulting fees from Edwards Lifesciences, consulting fees from Drager, consulting fees from General Electric Healthcare, lecture fees from Fresenius Kabi, and lecture fees from Baxter. MLeone declares COIs with Amomed (consulting, lecture), Aguettant (consulting), MSD (consulting, lecture), Pfizer (lecture), Aspen (lecture), Orion (lecture), Octapharma (lecture). PR is a co-founder of CardioRenal and declares personal fees (consulting) from Novartis, NovoNordisk, Relypsa, AstraZeneca, Grünenthal, Idorsia, Stealth Peptides, Fresenius, Vifor Fresenius Medical Care Renal Pharma, Vifor, and Clinical Trials Mobile Application; and lecture fees from Bayer and CVRx. AM reports personal fees from Novartis, Orion, Roche, Servier, Cardiorentis, Adrenomed, ZSPharma, Abbott, Neuro Tronik, Sphingotec, research grants from Critical diagnostics, MyCartis and Adrenomed; BD, EV, PC, and BP declare no conflict of interest. EG declares consultant fees from Magnisense and Adrenomed and research fees from Retia Medical, Deltex Medical, and Sphingotec.

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Figures

Fig. 1

SPIRIT schematic schedule of enrolment, interventions, and assessments

Fig. 2

Scheme of drug intake according to the treatment arm (experimental arm with continuation of the treatment or control arm with withholding of the drug 28 h before surgery). Profiles A, B, and C refer to the number of drug intakes across a day

Fig. 3

CONSORT flow chart of the study