Prevention of Post-operative Atrial Fibrillation by BOTulinum Toxin Injections Into Epicardial Fat Pads Around Pulmonary Veins in Patients Undergoing Cardiac Surgery"
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 220
- 试验地点
- 14
- 主要终点
- Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 weeks after cardiac surgery
研究概览
简要总结
Over the past few years, research has focused on the prevention of atrial fibrillation (AF) after cardiac surgery, but highly effective interventions are still missing. Postoperative AF remains the most common complication after cardiac surgery, with an incidence of 10 to 50%. This complication is usually a transient condition that resolves spontaneously but it has major adverse consequences for patients and the health care system, including increased rates of death, complications (strokes), and hospitalisations with inflated costs.
Recently, animal studies have demonstrated that neurotoxins such as botulinum toxin (BTX) injected into fat pads could suppress AF inducibility by parasympathetic activation. Botulinum toxin injection in fat pads has been studied in the dog's heart and could be associated with the reduction of atrial fibrillation in postoperative cardiac surgery. One pilot study has demonstrated the feasibility and safety of this technique in the human heart.
The investigators hypothesize that botulinum toxin injection may substantially reduce postoperative AF during the first postoperative month after cardiac surgery without any serious adverse events. By the suppression of ganglionic plexi (GP) activity in the epicardial fat pads, mild term antiarrhythmic effects can be achieved with fewer antiarrhythmic drugs and anticoagulant treatment.
详细描述
Botulinium toxin use has been developed with success in wide-ranging fields (neurology, otorhinolaryngology, gynaecology, urology, plastic surgery, pain therapy), but not in cardiology.
In the cardio-vascular field, only one pilot study on man has shown its utility in the prevention of atrial fibrillation by blocking the triggering through the sympathic and parasympathic systems. The investigators need to assess its potential benefits to prevent postoperative atrial tachyarrhythmia in a randomised multicentre study, with an expected impact of approximately 30,000 patients per years in France undergoing these types of cardiac surgery.
The investigators hypothesize that botulinum toxin injection may substantially reduce postoperative AF during the first 3 weeks after cardiac surgery without any serious adverse events. By the suppression of ganglionic plexi (GP) activity in the epicardial fat pads, mild term antiarrhythmic effects can be achieved with fewer antiarrhythmic drugs and anticoagulant treatment.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Indication for cardiac surgery (CABG, aortic valve repair or aortic valve replacement excluding the sutureless valve, ascending aorta surgery), according to the European Heart Association guidelines.
- •Patients in hemodynamically stable condition.
- •Sinus rhythm at moment of randomisation (ECG).
- •Age: ≥18 to ≤80 years old.
- •Negative serum or urinary β-hCG for women of child-bearing potential.
- •Patients able to attend several consultations at the centre.
- •Informed consent signed.
- •Affiliation to French social security regime.
排除标准
- •Previous cardiac surgery.
- •Persistent AF or atrial tachycardia.
- •Planned maze procedure or pulmonary vein (PV) isolation.
- •Use of class I or III antiarrhythmic drugs within 5 elimination half-life of the drug (for amiodarone: one year).
- •Mitral or tricuspid valve surgery.
- •Congenital cardiomyopathy.
- •Neuro-muscular disease (including disorders of pre-operative swallowing).
- •Protected populations e.g. minor patient, breastfeeding women, patients under legal guardianship, curatorship or legal protection. .
- •Participation in another interventional trial.
- •Unwillingness to participate.
- •Contraindications to botulinum toxin under investigation or to the excipients: known hypersensitivity.
- •Patient with active endocarditis Minimal invasive surgery (ministernotomy)
研究组 & 干预措施
Placebo
All patients from the control group will receive placebo. Before the main stage of the surgery, during extra corporal circulation and before aortic cross clamping, the placebo dissolved in 4 mL of 0.9% normal saline will be injected into the entire visible area of the 4 major epicardial fat pads as follows (1 mL at each fat pad).
干预措施: Drug placebo (Other)
Botulinum toxin
All patients from the experimental group will receive botulinum toxin (Xeomin®, incobotulinumtoxin A, Merz Pharma GmbH & Co KGaA, Germany; 200 U dissolved in 4 mL of 0.9% normal saline and 50 U/1 mL will be injected at each fat pad).
Botulinum toxin will be injected into the entire visible area of the 4 major epicardial fat pads, during extra corporal circulation and before aortic cross clamping in order to reduce the time of ischemia.
The whole estimated dosage would be therefore 200 units of incobotulinumtoxin A,
干预措施: Botulinum Toxin Type A Injection [Xeomin] (Drug)
结局指标
主要结局
Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 weeks after cardiac surgery
时间窗: 3 weeks
An episode of AF will be considered part of the primary outcome analyses if it last at least 30 seconds continuously within 21 days after cardiac surgery and is documented by any form of monitoring, regardless of symptoms. The definition of atrial fibrillation (at least 30 seconds continuously) results from recent publications and AF definition in the cardiovascular field64. This endpoint will be measured through both holter ECG Spiderflash-t recorder during the first 21 days post-op and ECG daily monitoring during the first 7 days after surgery.
次要结局
- Incidence of atrial tachyarrhythmia / Flutter(3 months)
- New onset of postoperative AF(3 months)
- Antiarrhythmic drugs(3 months)
- Death rate(12 months)
- Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 monthes after cardiac surgery(3 months)
- Number of patients presenting a cardiovascular event as conduction troubles, congestive heart failure, major bleeding, stroke, and arterial thromboembolic events(3 months)
- End of surgery until discharge (intervals from end of surgery to extubation, in hours)(10 days)
- Readmission rate(3 and 12 months)
- total hospital cost(twelve months)