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

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ClinicalTrials.gov Identifier: NCT03374449
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Renin Angiotensin System Surgery Procedure: continuation of the RAS-inhibitors Procedure: discontinuation of the RAS-inhibitors Not Applicable

Detailed 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.

Four follow-up visits are planned

  • Immediately after the surgery (Day 0)
  • Three 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2222 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The aim of this study is to evaluate the impact of Renin-Angiotensin System inhibitors management (Continuation or discontinuation 48 hours before surgery) on outcome in patients undergoing scheduled 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)
Masking: None (Open Label)
Masking Description: Endpoint validated by an adjudication commitee blinded to the arm.
Primary Purpose: Other
Official Title: Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery : a Multicenter, Prospective, Randomized and Controlled Trial
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : August 6, 2022
Estimated Study Completion Date : September 6, 2022

Arm Intervention/treatment
Experimental: continuation of the RAS-inhibitors
in the continuation of the RAS-inhibitors arm the treatment will be continued until the morning the day of surgery.
Procedure: continuation of the RAS-inhibitors
drug intake

Active Comparator: discontinuation of the RAS-inhibitors
In this arm : discontinuation of the RAS-inhibitors 48 hours before surgery Patients won't receive the drug on the morning of the day of the surgery.
Procedure: discontinuation of the RAS-inhibitors
no drug intake




Primary Outcome Measures :
  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; 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 Outcome Measures :
  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



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients requiring major non-cardiac surgery
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374449


Contacts
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Contact: Etienne Gayat, MD, PhD 01 49 95 55 83 ext +33 etienne.gayat@aphp.fr
Contact: Matthieu Legrand, MD, PhD 01 49 95 55 83 ext +33 matthieu.m.legrand@gmail.com

Locations
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France
Hospital Lariboisiere Recruiting
Paris, France, 75010
Contact: Etienne Gayat, MD,PhD    01 49 95 55 83 ext +33    etienne.gayat@aphp.fr   
Contact: Matthieu Legrand, MD,PhD    01 49 95 55 83 ext +33    matthieu.m.legrand@gmail.com   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Eienne Gayat, MD, PhD Hospital Laribioisière, APHP
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03374449    
Other Study ID Numbers: P160933J
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Major surgery
Postoperative morbidity and mortality
Renin angiotensin system inhibitors