Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery (STOPORNOT)

Assistance Publique - Hôpitaux de Paris

Status

Completed

Conditions

Surgery

Renin Angiotensin System

Treatments

Procedure: discontinuation of the RAS-inhibitors

Procedure: continuation of the RAS-inhibitors

Study type

Interventional

Funder types

Other

Identifiers

NCT03374449

P160933J

Details and patient eligibility

About

More than 200 million major surgical procedures are performed annually worldwide. Many of these patients have comorbidities including hypertension and/or heart failure. Chronic treatment of hypertension and/or heart failure very often includes a Renin-Angiotensin System (RAS) inhibitor (Angiotensin-Converting Enzyme Inhibitors (ACE-Is) or Angiotensin Receptor Blockers (ARBs). To stop or not to stop these medications before major surgery remain unknown. Data on management of RAS inhibitors before major surgery and anesthesia remain lacking and matter of debate. It is much likely that the strategy regarding management of RAS inhibitors in the peri-operative setting have important impact on peri-operative complications.

The lack of evidence leads to conflicting guidelines with respect to RAS inhibitors management before major surgery. While French guidelines are to stop RAS inhibitors patients with hypertension to avoid profound anesthestic-drugs-induced hypotension, international guidelines differ. The American heart association task force states that continuation of RAS inhibitors perioperatively is reasonable (class IIa recommendation,level of evidence: B). The purpose of this study is to determine the prognostic impact of withholding vs continuing ARBs before major non cardiac surgery.

Full description

Multicenter, prospective, randomized, pragmatic, parallel-group clinical trial. The inclusion visit takes place between 4 months and no later than 3 days before the surgery visit.

The randomization will be performed by the anesthesiologist Control group : RAS-I discontinuation Experimental group: RAS-I continuation
A prescription for the medication strategy (stopping or pursuing the medication) will be handed to the patient during the anesthesiology consultation.

Five follow-up visits are planned

Immediately, one hour after the surgery (Day 0)
Then four follow-up visits are planned on day 1, 2, 7 (or hospital discharge) and 28 days+15 days (43 days maximum) after surgery will be collected data and parameters for study endpoints.

End of research visit is the 28 days+15 days (43 days maximum) follow-up visit.

Enrollment

2,222 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients requiring major non-cardiac surgery (surgery with an expected duration of more than 2 hours from the surgical incision and a post-operative hospital stay of least 3 days) (according to the study RELIEF, DOI : 10.1056/NEJMoa1801601))
Age≥18 years
Patients chronically treated (>3 months before surgery) with RAS inhibitors
Pregnancy test at inclusion visit for women of childbearing potential Women of childbearing potential must agree to use adequate contraception according to Recommendations related to contraception and pregnancy testing in clinical trials, by Clinical Trial Facilitation Group (CTFG)
Signed informed consent

Exclusion criteria

Emergency surgery (surgical treatment needed within 24 hours)
Hyperkalemia (> 5.5mmol/L) known at the time of the anesthetic consultation
Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 1 month
Patient with severe renal insufficiency, known at the time of the anesthestic consultation (as defined by estimated glomerular filtration rate (creatinine clearance <15 ml/min/1.73m2 or requiring renal replacement therapy)
Patient with preoperative shock (defined by the need for vasoactive drugs before surgery)
Inability to obtain informed consent either from the patient.
Lack of Social Insurance