Abstract
BackgroundAtrial 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.MethodsEighty 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.DiscussionCurrent 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.Trial registrationClinicalTrials.gov, NCT03536806. Registered on 25 May 2018.
Highlights
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia which increases the risk of thromboembolic complications and impairs quality of life
According to ACC/AHA/HRS and ESC guidelines, application of class Ic and class III antiarrhythmic agents are recommended in pharmacological cardioversion of AF
AF might be induced by electrolyte, neurohormonal disorders, increased blood pressure, atrial volume overload and inflammatory states
Summary
Such protocols are not specified by the trial, but they include standard components, comprising clinical evaluation, plasma electrolyte level assessment, baseline 12-lead ECG performance, continuous ECG monitoring, periodic noninvasive blood pressure (BP) control and an intravenous line Rate control medications, such as β-blockers or calcium channel blockers (diltiazem, verapamil), are allowed in the previous 2 h before study intervention. Statistical analysis Comparison of categorical variables (sinus rhythm restoration, AF recurrence, serious adverse reactions, safety outcome) between groups will be performed using the χ2 test of independence with Yate’s correction, or with Fisher’s exact test in cases of minimum expected count less than 5, and these will be expressed as number and percentage. Statistical analysis will be conducted using SAS 9.2 software
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