Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery : a Multicenter, Prospective, Randomized and Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 2,222
- 试验地点
- 2
- 主要终点
- composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
Endpoint validated by an adjudication commitee blinded to the arm.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
composite outcome composed of all-cause mortality and major postoperative complications within 28 days after surgery.
时间窗: 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).
次要结局
- Maximum SOFA score(from postoperative day 1 to day 7)
- Hospital free-days(censored at 28 days following surgery)
- Acute kidney injury(after surgery until day 28)
- Episodes of hypotension(during anesthesia and surgery)
- Duration of hospital stay(after surgery until day 28)