A Randomized Active-Controlled Study Comparing Efficacy and Safety of Nifekalant to Amiodarone in New-Onset Atrial Fibrillation After Cardiac Surgery
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 274
- 试验地点
- 1
- 主要终点
- Rate of cardioversion at 4 hours
研究概览
简要总结
Postoperative atrial fibrillation is a major complication of cardiac surgery, which could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. New-onset atrial fibrillation after cardiac surgery is considered as a multifactorial phenomenon. Amiodarone, the most commonly used drug for cardioversion, is limited in atrial fibrillation after cardiac surgery due to side effects such as hypotension, bradycardia, and extracardiac side effects. Nifekalant is a novel class III antiarrhythmic agent with short onset time. It is a pure potassium channel blocker, which generally does not cause hypotension and bradycardia. There have been several trials that proven efficacy of nifekalant in converting persistent atrial fibrillation. For atrial fibrillation after cardiac surgery, the effectiveness and safety of nifekalant compared to amiodarone have not yet been reported. The investigators plan to perform a clinical trial comparing nifekalant to amiodarone in new-onset atrial fibrillation after cardiac surgery patients with a primary outcome of cardioversion at 4 hours. Secondary outcomes will follow cardioversion at 90 minutes and 24 hours, maintenance time of sinus rhythm within 24 hours, average time to conversion to sinus rhythm, rate of hypotension, length of ICU stay, length of hospital stay and hospital mortality.
详细描述
- Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia post cardiac surgery. Estimates suggest that rates of patients experiencing AF after cardiac surgery exceeds 30%. AF has multiple effects on the cardiopulmonary hemodynamics. New-onset atrial fibrillation after cardiac surgery is considered as a multifactorial phenomenon. Its pathogenesis is characterized by inflammation, oxidative stress and autonomic dysfunction. AF after cardiac surgery could lead to high morbidity and mortality, increase duration of hospital stay and increase the cost of treatment. Treatment of AF include rhythm control and rate control. Typical rate control agents are contraindicated due to need of vasoactive requirements. The 2017 EACTS Guidelines on perioperative medication in adult cardiac surgery recommends that in patients with hemodynamically stable postoperative AF, rhythm control is recommended (I, B). Currently, amiodarone is most commonly used drug for rhythm control. It has long onset and cardioversion time. It can also cause side effects such as hypotension, typically requiring escalating doses of vasoactive medications. Other side effects include bradycardia, and extracardiac side effects in lung, liver and thyroid, which limit the clinical application of amiodarone in AF after cardiac surgery. Nifekalant is a novel class III antiarrhythmic agent with short onset time. It is a pure potassium channel blocker, which generally does not cause hypotension and bradycardia. Nifekalant prolongs the action potential duration and effective refractory period of atrial and ventricular myocytes, and prolong the QT interval. There have been several trials that proven efficacy of nifekalant in converting persistent atrial fibrillation. For new-onset AF post cardiac surgery, the effectiveness and safety of nifekalant compared to standard of care amiodarone have not yet been reported.
- Research hypothesis: For patients with new-onset atrial fibrillation after cardiac surgery, administration of nifekalant is not inferior to amiodarone in terms of rate of cardioversion to sinus rhythm at 4 hours.
- Methods: Patients after cardiac surgery will be recruited from the ICU based on inclusion and exclusion criteria. Patients identified with new-onset atrial fibrillation with a sustained duration of greater than 1 minutes and less than 48 hours will be considered for the study. Patients will be randomized to amiodarone versus nifekalant using a computerized process. The primary outcome is rate of cardioversion at 4 hours. Secondary outcomes include rates of cardioversion at 90 minutes and 24 hours, maintenance time of sinus rhythm within 24 hours, average time to cardioversion to sinus rhythm, rate of hypotension, length of ICU stay, length of hospital stay and hospital mortality.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old, <85 years old, no gender limit;
- •Postoperative atrial fibrillation in the ICU after cardiac surgery;
- •The duration of atrial fibrillation> 1 minute, and ≤ 48 hours;
- •Hemodynamically stable (no need to increase vasoactive drugs and SBP>90/MAP>60mmHg);
- •After pre-treatment (including: correcting electrolyte disturbances, optimizing volume status, improving oxygenation, controlling body temperature, analgesia and minimizing the use of inotropes and vasopressors), the clinician believes that antiarrhythmic drugs are needed.
- •Obtained the informed consent from the patients or their family members.
排除标准
- •Heart transplantation, left heart assist device (LVAD) or extracorporeal membrane oxygenation (ECMO) treatment;
- •History of atrial fibrillation/atrial flutter and a history of paroxysmal supraventricular tachycardia;
- •Radiofrequency ablation;
- •Rheumatic heart disease;
- •Complex congenital heart disease (with more than two coexisting congenital heart defects);
- •Cardiac tumors;
- •Transcatheter aortic valve implantation (TAVI), transcatheter mitral valve intervention (TMVI), and transcatheter tricuspid valve intervention (TTVI);
- •Contraindications to amiodarone/nifekalant (PR interval>240ms; 2nd or 3rd degree atrioventricular block (AVB); QT>440ms; familial long QT syndrome; Untreated thyroid disease; AST or ALT>2 times the upper limit; liver cirrhosis; interstitial lung disease);
- •Heart rate (HR) <50 beats/min and/or QRS>140ms without a pacemaker;
- •Received amiodarone or nifekalant within 6 weeks before the operation;
- •Pregnant and lactating female patients;
- •Uncorrected hypokalemia (serum potassium <3.5mmol/L) or hypomagnesemia (whole blood/serum magnesium below the lower limit);
- •Chronic renal failure and/or continuous renal replacement therapy (CRRT);
- •Return to OR during ICU stay or readmission to ICU from Cardiac Surgery ward.
- •Other factors not suitable for participating in this study
研究组 & 干预措施
Intravenous Nifekalant
Patients randomized to Nifekalant arm will receive a bolus of 0.3mg/kg IV in the first 5 minutes and a maintenance dose of 0.2-0.4mg/kg/h for 24 hours. If the patient has a recurrence of atrial fibrillation, the maintenance dose can be increased (up to 0.8 mg/kg/h) according to the patient's condition, or receive a bolus of 3mg/kg again at 2 hours intervals. Nifekalant is administered for 24 hours unless meeting the criteria for discontinuation.
干预措施: Nifekalant (Drug)
Intravenous Amiodarone
Patients randomized to an amiodarone arm will receive a bolus of 150mg IV in the first 10 minutes and a maintenance dose of 0.5-1mg/min for 24 hours. If the patient has a recurrence of atrial fibrillation, the dosage can be adjusted according to the patient's condition, but the total dosage administered within 24 hours should not exceed 2g. Amiodarone is administered for 24 hours unless meeting the criteria for discontinuation.
干预措施: Amiodarone (Drug)
结局指标
主要结局
Rate of cardioversion at 4 hours
时间窗: 4 hours
Rate of cardioversion of new-onset atrial fibrillation at 4 hours. The rate of cardioversion = the number of patients who meet the cardioversion criteria in the group / the total number of patients in the group × 100%. Cardioversion criteria is: atrial fibrillation stops at least once during the 24 hours observation period and lasts for more than 1 minute.
次要结局
- Average time to AF conversion to sinus rhythm(24 hours)
- Incidence of severe bradycardia, 3rd degree AVB, severe ventricular arrhythmia(24 hours)
- Rate of cardioversion at 24 hours(24 hours)
- Maintenance time of sinus rhythm within 24 hours(24 hours)
- Rate of cardioversion at 90 minutes(90 minutes)
- Vasoactive Inotropic Score (VIS) at 90 minutes, 4 hours, and 24 hours(24 hours)
- Liver and kidney function within 24 hours(24 hours)
- Hospital mortality(up to 6 months)
- The incidence of hypotension(24 hours)
- Cardiac function(24 hours)
- Co-administration of drugs(24 hours)
- Adverse events(24 hours)
- Days of hospital stay(up to 6 months)
- Length of ICU stay(up to 6 months)
研究者
Xiaotong Hou
Professor
Beijing Anzhen Hospital