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NCT Number: NCT03374449

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

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.

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Key information

Conditions

Renin Angiotensin System Surgery

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hospital Lariboisiere

Paris, 75010, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

continuation of the RAS-inhibitors

Procedure

drug intake

discontinuation of the RAS-inhibitors

Procedure

no drug intake

Primary outcomes

  1. composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery.

    Time frame: after surgery until day 28

    Complications will be validated by an adjudication committee, blinded to the treatment arm.

    Death; Acute Myocardial infarction; Arterial or venous thrombosis; Stroke; Acute pulmonary oedema; Post-operative cardiogenic shock; Acute severe hypertension crisis; Cardiac arrhythmia requiring therapeutic intervention; Postoperative episodes of sepsis; Postoperative respiratory complication; Need for unplanned intensive care unit admission or readmission; Acute kidney injury: KDIGO criteria Baseline serum creatinine is obtained from the pre-operative blood sample; Surgical complications: need for reoperation for any reason and radiologic interventions for abscess drainage; Severe Hyperkalemia: serum potassium level >5.5 mmol/L and requiring therapeutic intervention (insulin/glucose infusion and/or sodium bicarbonate infusion and/or intravenous B2 agonists and/or intravenous calcium gluconate and/or renal replacement therapy and/or ventricular tachycardia or ventricular fibrillation).

Secondary outcomes

  1. Episodes of hypotension

    Time frame: during anesthesia and surgery

    Episodes requiring vasopressors administration

  2. Acute kidney injury

    Time frame: after surgery until day 28

    according to the KDIGO criteria

  3. Maximum SOFA score

    Time frame: from postoperative day 1 to day 7

    patients admitted to ICU

  4. Duration of hospital stay

    Time frame: after surgery until day 28

    Patients who will be outside the hospital but in other types of health care facilities at day 28 will be considered to have been discharged home

  5. Hospital free-days

    Time frame: censored at 28 days following surgery

    Duration after hospital discharge

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery : a Multicenter, Prospective, Randomized and Controlled Trial

Acronym: STOPORNOT

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Dec 15, 2017
Registry last updated
May 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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