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
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|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2222 participants|
|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.|
|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|
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
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
- 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).
- 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
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
|Contact: Etienne Gayat, MD, PhD||01 49 95 55 83 ext +email@example.com|
|Contact: Matthieu Legrand, MD, PhD||01 49 95 55 83 ext +firstname.lastname@example.org|
|Principal Investigator:||Eienne Gayat, MD, PhD||Hospital Laribioisière, APHP|