National Institute of Cardiology, ul. Alpejska 42, Warsaw, 04-628, Poland.
Trials. 2020 May 12;21(1):397. doi: 10.1186/s13063-020-04277-3.
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia which increases the risk of thromboembolic complications and impairs quality of life. An important part of a therapeutic approach for AF is sinus rhythm restoration. Antiarrhythmic agents used in pharmacological cardioversion have limited efficacy and potential risk of proarrhythmia. Simultaneously, underlying conditions of AF should be treated (e.g. electrolyte imbalance, increased blood pressure, neurohormonal disturbances, atrial volume overload). There is still the need for an effective and safe approach to increase AF cardioversion efficacy. This randomized, double-blind, placebo-controlled, superiority clinical study is performed in patients with AF in order to evaluate the clinical efficacy of intravenous canrenone in sinus rhythm restoration.
Eighty eligible patients with an episode of AF lasting less than 48 h are randomized in a 1:1 ratio to receive canrenone or placebo. Patients randomized to a treatment intervention are receiving canrenone intravenously at a dose of 200 mg within 2-3 min. Subjects assigned to a control group obtain the same volume of 0.9% saline within the same time. The primary endpoint includes return of sinus rhythm documented in the electrocardiogram within 2 h after drug or placebo administration. Other endpoints and safety outcomes analyses, due to expected lack of statistical power, are exploratory.
Current evidence supports renin-angiotensin-aldosterone system (RAAS) inhibition as an upstream therapy in AF management. Excess aldosterone secretion results in proarrhythmic effects. Among the RAAS inhibitors, only canrenone is administered intravenously. Canrenone additionally increases the plasma level of potassium, lowers blood pressure and reduces preload. It has been already used in primary and secondary hyperaldosteronism in the course of chronic liver dysfunction and in heart failure.
ClinicalTrials.gov, NCT03536806. Registered on 25 May 2018.
心房颤动（AF）是最常见的心律失常，会增加血栓栓塞并发症的风险，并降低生活质量。AF 治疗方法的一个重要部分是恢复窦性心律。用于药物电复律的抗心律失常药物疗效有限，且有致心律失常的潜在风险。同时，还应治疗 AF 的潜在病因（如电解质失衡、血压升高、神经激素紊乱、心房容积超负荷）。仍需要一种有效且安全的方法来提高 AF 电复律的疗效。这项随机、双盲、安慰剂对照、优效性临床研究旨在评估静脉用坎地沙坦恢复窦性心律的临床疗效。
将 80 名 AF 发作持续时间<48 h 的合格患者以 1:1 的比例随机分为坎地沙坦组或安慰剂组。随机接受治疗干预的患者在 2-3 分钟内静脉给予坎地沙坦 200mg。对照组患者在相同时间内接受相同容量的 0.9%生理盐水。主要终点包括在药物或安慰剂给药后 2 h 内心电图记录的窦性心律恢复。由于预期缺乏统计学效能，其他终点和安全性结果分析均为探索性分析。
目前的证据支持肾素-血管紧张素-醛固酮系统（RAAS）抑制作为 AF 管理的上游治疗。醛固酮分泌过多会导致心律失常。在 RAAS 抑制剂中，只有坎地沙坦可静脉给药。坎地沙坦还可增加血钾水平、降低血压和减少前负荷。它已在慢性肝功能障碍和心力衰竭中用于原发性和继发性醛固酮增多症。
ClinicalTrials.gov，NCT03536806。注册于 2018 年 5 月 25 日。
