Spironolactone and Perioperative Atrial Fibrillation Occurrence in Cardiac Surgery Patients: a Multicenter Randomized, Double-blind Study. The ALDOCURE Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 1,500
- 试验地点
- 2
- 主要终点
- POAF occurrence
研究概览
简要总结
Study hypothesis : Pre-operative aldosterone receptor blockade may reduce post-operative atrial fibrillation (POAF) occurrence within 5 days after coronary artery bypass graft surgery (CABG) ± aortic valve replacement (AVR) without any heart failure or any mitral surgery.
Primary efficacy criterion : occurrence of POAF occurring from randomization and within 5 days after surgery, assess, in a standardized manner, by continuous ECG monitoring (during the ICU stay) or Holter-ECG monitoring (during the stepdown unit stay).
Primary objective: To establish whether pre-operative administration of spironolactone leads to a reduction in POAF incidence occurring from randomization and within 5 days after surgery, compared with placebo, in patients referred for on-pump elective CABG surgery ± AVR without heart failure.
Study design : Phase III drug trial - Randomized, double blind, multicentre, prospective study.
详细描述
Introduction:
Despite advances in surgical and perioperative care, postoperative complications after cardiac surgery remain frequent, leading to substantial increases in mortality, morbidity, and costs. Postoperatively, 30% of patients who underwent coronary artery bypass graft (CABG) present atrial fibrillation (AF). The presence of POAF is associated with a greater short and long term cardiovascular morbidity and mortality (death, stroke, heart failure, myocardial infarction) and is at the origin of a significant increase in hospitalization stay.
The mechanisms underlying POAF are multifactorial and complex but require at least the presence of an arrhythmogenic substrate, cardiac fibrosis and electrical remodelling. Aldosterone is a key component in this context. The link between aldosterone, cardiac fibrosis and adverse electrical remodelling is now very well established and a significant association between plasma aldosterone levels, MRA and AF incidence is now well established.
In a preliminary study, the investigators established the relationship between preoperative plasma aldosterone levels and post-operative AF occurrence in patients addressed for CABG without any systolic heart failure or mitral valve surgery associated (NCT 02814903). The investigators have thus demonstrated that plasma aldosterone levels were strongly predictive of post-operative AF occurrence. These results permitted to establish a risk score called "Aldoscore" (including the patient's age and the aldosterone level) to detect patients at high risk to develop post-operative AF. The investigators also validated this score in an independent and external Japanese population issued from the NU-HIT trial.
Investigators propose to perform a randomized, multicenter, double-blind versus placebo study to evaluate the efficacy of spironolactone administrated 14 days before heart surgery and continued during 30 days after surgery, on POAF incidence in patients referred for CABG without any heart failure or mitral valve surgery associated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female; Age ≥ 18 years
- •On-pump elective CABG surgery ± AVR
- •In sinus rhythm
- •Patient signed consent
- •Willing to comply with scheduled visits, as outlined in the protocol
- •French nationality
- •Recipients of the social security regime
排除标准
- •Contraindications to spironolactone therapy: intolerance, hyperkalemia (>5.0 mmol/L), severe renal dysfunction (defined as an estimated glomerular filtration rate (eGFR) < 30 ml/min. Subjects with serum creatinine ≥2.5 mg/dl are also excluded even if their eGFR is ≥30 ml/min), Severe liver dysfunction (Child-Pugh Class 3), patients treated by other potassium sparing medication (except in case of hypokalemia).
- •Patients treated by MRA treatment (spironolactone or eplerenone)
- •LVEF < 50% obtained within 6 months prior to V0
- •Mitral valve surgery associated to the CABG
- •Off-pump beating or emergent/urgent CABG
- •History of AF or another atrial arrhythmia
- •Presence of antiarrhythmic medication (other than β-blockers)
- •Previous heart surgery and heart transplant recipient
- •Unstable conditions: angina or acute coronary syndrome or heart failure during the last 3 months, cardiogenic shock
- •Patients included or planning to be included in another medical research protocol
- •Patients unable to complete the protocol follow-up
- •Pregnant or nursing women
- •Adults with protective measures (curatorship or tutorship or safeguarding justice or juridical protection)
研究组 & 干预措施
Reference treatment
干预措施: Placebo oral capsule (Drug)
experimental treatment
Spironolactone 25 mg
干预措施: Spironolactone 25mg (Drug)
结局指标
主要结局
POAF occurrence
时间窗: 5 days
the occurrence of POAF occurring from randomization and within 5 days after surgery, assess, in a standardized manner, by continuous ECG monitoring (during the ICU stay) or Holter-ECG monitoring (during the stepdown unit stay).
次要结局
- Post-operative AF occurrence from cardiac surgery and within 5 days after CABG surgery (+/- AVR),(5 days)
- Evaluation of perioperative myocardial injury within 2 days after surgery, as assessed by serial measurements of the cardiac troponin I concentration at day 0 immediately after surgery, day 1 and 2 after surgery,(2 days)
- Occurrence of major cardiovascular events and death (death from any cause, stroke, heart failure, myocardial infarction) occurring within 30 days after surgery,(30 days)
- Duration of ICU and hospital stay,(30 days)
- Evaluation of the LVEF at discharge (from both ICU and hospital discharge),(30 days)
- Need for readmission,(30 days)
- Ventricular arrhythmia occurring from cardiac surgery and within 5 days after surgery, assess, in a standardized manner, by continuous ECG monitoring (during the ICU stay) or Holter-ECG monitoring (during the stepdown unit stay),(5 days)
- Occurrence of low blood pressure (both systolic and diastolic), changes in serum potassium and acute kidney injury within 30 days after surgery.(30 days)