A Prospective, Randomized, Double- Blind, Placebo- Controlled Study to Evaluate the Efficacy of Landiolol Hydrochloride for Prevention of Atrial Fibrillation in Patients Undergoing Cardiac Surgery
试验速览
- 阶段
- 3 期
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- The primary end point is a combined endpoint consisting of the occurrence of atrial fibrillation and mortality during the initial 72 hours period after surgery
研究概览
简要总结
Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery with incidences ranging from 20% to 40% with the consequence of increasing mortality, morbidity, and hospital length of stay, as well as increasing the costs to the health care system. To prevent POAF the use of beta-blockers is suggested by the EACTA and ESC guidelines. Despite the prophylactic use, the discontinuation of beta-blockers in the perioperative period is a known risk factor that contributes to the occurrence of POAF. Due to the short half time and the highly beta-1-selective properties of Landiolol, it could be possible to initiate a betablocker for prevention in the immediate postoperative setting, without adverse effects like hypotension or severe bradycardia as seen with other betablockers like Metoprolol or even sometimes Esmolol.
Landiolol is already approved for the treatment of atrial tachycardias but is not yet approved for the use of prevention of POAF. In multiple previous studies the preventive potential of Landiolol in cardiac surgery could be proven in japanese study populations, with limitations due to limited sample sizes. In these trials the use of low-dose Landiolol effectively reduced the incidence of POAF without significant differences of increased side effects or in the hemodynamic stability compared to the placebo or standard of care groups.
The primary objective of this prospective, double-blind, randomized, placebo-controlled phase III trial is to prove that the postoperative application of low-dose Landiolol significantly reduces the incidence of POAF without increased adverse events or hemodynamic instability compared to the placebo group after cardiac surgery in a non-Asian population.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female patients ≥ 18 years old
- •Written informed consent from patient
- •Patients are in sinus rhythm
- •Oral Betablocker in the patients long-term medication
- •One of the following cardiac surgical procedures which is planned on cardiopulmonary bypass (CPB):
- •Single valve surgery
- •Single or multiple CABG procedures
- •Single valve surgery in combination with one or multiple coronary artery bypass grafts (CABGs)
- •Multiple valve surgery in combination with or without CABG
- •Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG
- •Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG
- •Cardiac surgery is performed electively
排除标准
- •Bodyweight > 101kg and/or BMI ≥ 40
- •Cardiac surgery is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy) or planned as off-pump surgery
- •Planned maze procedure, radiofrequency ablation, pulmonary vein ablation, resection of the atrial appendix or atrial resections during the surgery
- •Sinus bradycardia (resting heart rate < 50/min) at screening and before start of IMP treatment
- •Second- or third-degree atrioventricular block at screening and before start of IMP treatment
- •Clinical hypothyroidism or hyperthyroidism at screening
- •History of ventricular arrhythmia
- •Permanent atrial fibrillation or atrial fibrillation at time of screening and IMP administration
- •Emergency cardiac surgery
- •Requiring inotropic, vasopressor or requiring ventilatory support at time of screening
- •Circulatory shock requiring mechanical circulatory support before initiation of study medication
- •Distributive shock (cardiac index>2.2 L/min with norepinephrine dose > 0.3 µg/kg/min to reach mean arterial pressure > 65mmHg) before initiation of study medication
- •More than 5 units of RBC necessary to maintain a haemoglobin level >8mg/dl at the end of surgery
- •Prior cardiac surgery within the past 6 months
- •History of heart transplantation or planned heart transplantation
- •Any other disease or condition that is likely to interfere with the evaluation of the study drug, outcome assessment or satisfactory conduct of the study:
- •Active infective endocarditis
- •Stroke or transient ischemic attack (TIA) within the last 6 months
- •Concomitant disease with a life expectancy of less than 6 months
- •Cardiopulmonary resuscitation within the last 4 weeks
- •Patients requiring renal replacement therapy
- •Active infection on current systemic antibiotics and/ or temperature greater than 38°C at time of screening and before start of surgery
- •Haemoglobin < 5 mmol/l (< 8.06 g/dl)
- •Any systemic anti-cancer therapy within past 3 months
- •Patients with known hypersensitivity to any constituent of the IMP
- •General exclusion criteria:
- •Pregnant (in women of childbearing potential a urine or blood pregnancy test has to be performed) or breast-feeding women. Women with childbearing potential (defined as within two years of their last menstruation) not willing to practice appropriate contraceptive measures (e.g., implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy, abstinence) while participating in the trial
- •Participation in any interventional clinical trial within the last one-month prior randomization in this clinicaltrial (screening failures can be rescreened, if appropriate)
- •Alcohol, drug, or medication abuse
- •Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, subinvestigators, or study nurse) or relationship to the sponsor
研究组 & 干预措施
Landiolol group
Randomized patients receiving low dose landiolol after cardiac surgery
干预措施: Landiolol HCl (Drug)
Placebo group
Randomized patients receiving 0,9% saline solution after cardiac surgery
干预措施: Placebo (Drug)
结局指标
主要结局
The primary end point is a combined endpoint consisting of the occurrence of atrial fibrillation and mortality during the initial 72 hours period after surgery
时间窗: 3 days
Death from any reason or the occurence of atrial in the holter ecg within 3 days after operation.
次要结局
- Incidence/ frequency of occurrence of atrial fibrillation during the first seven days after cardiac surgery(7 days)
- Requirement of intensive respiratory and circulatory support(30 days)
- Peri- and postoperative mortality(30 days)
- Echocardiographic assessment for left ventricular function(7 days)
- Hemodynamic stability during treatment with IMP(7 days)
- Length of ICU stay(30 days)
- Assessment of biomarkers as surrogate parameters for cardiac dysfunction(30 days)
- Biomarker Assessment for cardiac injury, remodelling and fibrosis(7 days)
- Incidence of serious adverse events(30 days)
研究者
Andreas Binder
Prinicipal Investigator
Medical University of Vienna