Clinical Efficacy of Potassium Canrenoate - Canrenone in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation and Elevated Blood Pressure - a Pilot Randomized Controlled Trial.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 80
- 主要终点
- Conversion of atrial fibrillation to sinus rhythm.
研究概览
简要总结
The purpose of this randomized, double blind, placebo-controlled, superiority clinical trial was to assess clinical efficacy of potassium canrenoate - canrenone in rapid conversion of atrial fibrillation to sinus rhythm.
详细描述
Canrenone is a specific antagonist of aldosterone. It is a competitive inhibitor of aldosterone receptors and inhibits the effects of aldosterone. Spironolactone is a prodrug which is active after its conversion into canrenone. By inhibiting the effects of aldosterone it increases aqueous and sodium diuresis and is classified as a diuretic. It decreases urinary elimination of potassium and increases urinary excretion of calcium. Canrenone is used for the treatment of primary or secondary hyperaldosteronism, edema and ascites of congestive heart failure and cirrhosis, and in the treatment of the arterial hypertension. Current evidence supports renin-angiotensin-alodsterone (RAAS) inhibition: angiotensin-converting-enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) or, potentially, mineralocorticoid receptor antagonists (MRA) as an upstream therapy for atrial fibrillation (AF) management. It has been demonstrated that plasma aldosterone concentration may be increased in patients with AF episode, and it lowers after cardioversion. Only canrenone (potassium canrenoate) may be administered intravenously. Canrenone increases plasma level of potassium, lowers blood pressure and reduces preload at the same time.
To show superiority of canrenone over placebo a sample size of 80 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of canrenone 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.
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
- Double (Participant, Care Provider)
盲法说明
Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •written informed consent for enrolment
- •patients aged between 40 and 75 years
- •atrial fibrillation episode lasting for less than 48 hours, documented by the ECG
- •potassium plasma levels < 4.5 mmol/l
- •blood pressure > 120/80 mmHg
- •stable cardiopulmonary status (according to attending physician's assessment)
- •in case of left ventricle injury suspicion or unclear medical history of cardiac insufficiency, enrolment will be possible after echocardiographic examination
排除标准
- •no written informed consent for enrollment
- •allergy to canrenone
- •cardiac insufficiency or LVEF (left ventricular ejection fraction) < 40%
- •systolic BP < 120/80 mmHg
- •history of canrenone treatment in the 30 days before enrollment
- •average QRS rate > 160 p.m.
- •advanced hepatic or renal failure
- •history of acute coronary syndrome, CABG (coronary artery bypass grafting), TIA (transient ischemic attack) or stroke within the previous 30 days
- •pre-excitation syndrome (which has not been treated with accessory pathway ablation).
- •atrial fibrillation due to a valvular heart disease
- •atrial fibrillation episode resulting in myocardial ischemia (chest pain, ischemic changes in the ECG)
研究组 & 干预措施
Placebo Comparator: Placebo
Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. After drug administration the patient will be observed for 2 hours after the last dose with exit ECG and BP measure taken at the end of observation. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines.
干预措施: Saline 0.9% (Drug)
Experimental: canrenone
Any patient fulfilling the inclusion criteria will be prepared to pharmacological cardioversion in a standard way comprising of standard baseline 12-lead ECG, continuous ECG monitoring, periodic noninvasive blood pressure monitoring (BP) and iv line. After administration of canrenone: dose 200 mg (1 ampule a 10 ml) within 2-3 minutes the patient will be observed for 2 hours after the dose with exit ECG and BP measure taken at the end of observation.
干预措施: Canrenone (Drug)
结局指标
主要结局
Conversion of atrial fibrillation to sinus rhythm.
时间窗: Time Frame: 2 hours.
Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.
次要结局
- Time to conversion of atrial fibrillation to sinus rhythm.(Time Frame: 2 hours.)
- Serious adverse reactions.(Time Frame: 24 hours.)
- Safety outcome (exploratory analysis).(Time Frame: 24 hours.)
- Atrial fibrillation recurrence within observation period.(Time Frame: 2 hours.)
研究者
Rafał Dąbrowski
Rafal Dabrowski, MD, PhD
National Institute of Cardiology, Warsaw, Poland