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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

Tracking Information
First Submitted Date  ICMJE December 11, 2017
First Posted Date  ICMJE December 15, 2017
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE February 6, 2018
Estimated Primary Completion Date August 6, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • Episodes of hypotension [ Time Frame: during anesthesia and surgery ]
    Episodes requiring vasopressors administration
  • Acute kidney injury [ Time Frame: after surgery until day 28 ]
    according to the KDIGO criteria
  • Maximum SOFA score [ Time Frame: from postoperative day 1 to day 7 ]
    patients admitted to ICU
  • 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
  • Hospital free-days [ Time Frame: censored at 28 days following surgery ]
    Duration after hospital discharge
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery
Official Title  ICMJE Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery : a Multicenter, Prospective, Randomized and Controlled Trial
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE
  • Renin Angiotensin System
  • Surgery
Intervention  ICMJE
  • Procedure: continuation of the RAS-inhibitors
    drug intake
  • Procedure: discontinuation of the RAS-inhibitors
    no drug intake
Study Arms  ICMJE
  • 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.
    Intervention: Procedure: continuation of the RAS-inhibitors
  • 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.
    Intervention: Procedure: discontinuation of the RAS-inhibitors
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 14, 2017)
2222
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 6, 2022
Estimated Primary Completion Date August 6, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03374449
Other Study ID Numbers  ICMJE P160933J
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eienne Gayat, MD, PhD Hospital Laribioisière, APHP
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP