Interest of Low-dose Landiolol Administration After Cardiac Surgery for the Prevention of Postoperative Atrial Fibrillation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 400
- 试验地点
- 3
- 主要终点
- POAF occurrence in Intensive Care Unit (ICU)
研究概览
简要总结
Postoperative atrial fibrillation (POAF) is a common complication that occurs in 30-50% of patients after cardiac surgery and increases morbidity and mortality and hospital length of stay. During the perioperative period, the discontinuation of beta-blocker treatment is known to be a risk factor for developing POAF in patient undergoing cardiac surgery. Early beta-blocker reintroduction is associated with lower incidence of POAF. Unfortunately, side effects of currently available beta-blockers (including esmolol), such as low blood pressure and excessive bradycardia and/or their extended duration of action, limit their use in the post-operative period especially for prevention.
Landiolol, an ultra-short acting injectable beta-blocker, offers the advantage of significantly limiting low blood pressure events while increasing therapeutic efficacy in the treatment of POAF in cardiac and non-cardiac surgery. Landiolol, when used at low dose in the postoperative period, has been showed to reduce the incidence of POAF with no increased incidence of side effect as compared to standard of care. The limitation is that these promising data come from single center studies with limited samples and conducted exclusively in Japanese population. If landiolol is approved for use in the treatment of atrial fibrillation in non-Asian patients, there are no data on the prevention of POAF in cardiac surgery.
The objective of this multicenter, double-blind, randomized, placebo- controlled phase III trial is to confirm that landiolol postoperative infusion is associated with lower incidence of POAF without excess of adverse events as compared to standard of care in a non-Asian population after cardiac surgery with sternotomy.
详细描述
This is a multicenter, randomized, double-blind, parallel-group controlled, Landiolol vs Placebo (saline), phase III trial assessing the efficacy and the safety of landiolol postoperative treatment on POAF occurrence within 7 days of surgery in patients undergoing cardiac surgery with sternotomy.
Subjects are randomly assigned in a 1:1 ratio to receive either Landiolol or Placebo (saline). A stratification of the randomization is planned according to the hospital and the age of the patient (65 ≤ age ≤ 70 and age > 70).
A preventive treatment is infused during at least the first 24 hours after surgery (in ICU) to each patient included in the study until the optimal oral betablocker dose. Continuous infusion of landiolol at 2 µg/kg/min (1.2 ml/h, for a 60 kg patient) in Landiolol group or continuous infusion of saline (at 1.2 ml/h for a 60 kg patient) in Placebo group is administrated until restoration of an effective oral beta-blocker treatment.
Treatment:
Treatment is initiated after the surgery, on arrival at the ICU (Day-0) in the absence of a contraindication. The target of continuous intravenous infusion of landiolol is 2 µg/kg/min (1.2 ml/h for a 60 kg patient), or placebo (saline) at the same infusion rate as landiolol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-Asian,
- •Undergoing cardiac surgery with CPB,
- •Left ventricular ejection fraction (LVEF) ≥ 40%,
- •Having signed a written informed consent form,
- •Affiliation to the social security system.
- •Preoperative
排除标准
- •Paroxystic or persistant atrial fibrillation before surgery,
- •Preoperative contraindication to beta-blockers,
- •Known hypersensitivity to landiolol,
- •Severe conduction disorders (atrio-ventricular conduction block),
- •A mental or linguistic inability to understand the study,
- •Dying patient,
- •Patient under protection of the adults (guardianship, curators or safeguard of justice),
- •Patient included or planning to be included in another research protocol relating to medications.
- •Postoperative Exclusion Criteria:
- •Postoperative contraindication to beta-blockers: severe sinus bradycardia requiring pacing, postcardiotomy low cardiac output requiring inotropic agents (noradrenaline being not considered as an inotropic agent), severe hypotension, severe acute pulmonary hypertension, reoperation for significant bleeding (> 200 ml/h), acute respiratory distress syndrome defined by increased oxygen dependence, a PaO2/FiO2 ratio < 200, polypnea > 30 /min, signs of respiratory distress (retractions, thoraco-abdominal asynchrony).
研究组 & 干预措施
Landiolol group
Landiolol infusion (2µg/kg/min) administrated after the surgery, on arrival at the ICU, until restoration of an effective oral beta-blocker treatment.
干预措施: Landiolol (Drug)
Placebo group
Saline solution infusion administrated after the surgery, on arrival at the ICU, until restoration of an effective oral beta-blocker treatment.
干预措施: Saline (Drug)
结局指标
主要结局
POAF occurrence in Intensive Care Unit (ICU)
时间窗: 7 days
POAF event occurring from arrival to departure of the ICU assessed by continuous monitoring of heart rate (HR). POAF is defined as the occurrence of atrial fibrillation de novo, lasting more than 5 minutes (on the systematic reading of telemetry) and/or requiring specific medical treatment and/or cardioversion.
次要结局
- Need for cardioversion for POAF treatment(30 days)
- Need for medical treatment for POAF treatment(30 days)
- Duration of POAF episode(30 days)
- Day-30 POAF free days(30 days)
- Delay between ICU admission and the first event of POAF(30 days)
- Day-30 ICU free days(30 days)
- Day-30 ventilator-free days(30 days)
- Delay for discharge because of POAF event(30 days)
- Day-30 hospital free days(30 days)
- Day-30 renal replacement therapy-free days(30 days)
- In-ICU death(30 days)
- Occurrence of major cardiovascular events(30 days)
- Occurrence of drug adverse events(7 days)
- Total hospital cost(30 days)
- Delay between the first event and the recidive of POAF(30 days)
- All-cause mortality(30 days)
- In-hospital death(30 days)