Clinical trial NCT03536806: Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation.
Official title: Clinical Efficacy of Potassium Canrenoate - Canrenone in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation and Elevated Blood Pressure - a Pilot Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atrial Fibrillation, Paroxysmal
Keywords: Pharmacological cardioversion
Canrenone
Lead sponsor: National Institute of Cardiology, Warsaw, Poland
Sponsor class: OTHER
First posted: 2018-05-25
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Conversion of atrial fibrillation to sinus rhythm.
timeFrame: Time Frame: 2 hours.
Secondary outcomes:
measure: Time to conversion of atrial fibrillation to sinus rhythm.
timeFrame: Time Frame: 2 hours.
measure: Atrial fibrillation recurrence within observation period.
timeFrame: Time Frame: 2 hours.
measure: Serious adverse reactions.
timeFrame: Time Frame: 24 hours.
measure: Safety outcome (exploratory analysis).
timeFrame: Time Frame: 24 hours.
Other outcomes:
Locations:
Study officials:
affiliation: Institute of Cardiology
name: Rafał Dąbrowski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Cardiology
name: Tomasz Hryniewiecki, MD, PhD
role: STUDY_CHAIR
References:
citation: Dabrowski R, Syska P, Maczynska J, Farkowski M, Sawicki S, Kubaszek-Kornatowska A, Michalek P, Kowalik I, Szwed H, Hryniewiecki T. Clinical efficacy of potassium canreonate-canrenone in sinus rhythm restoration among patients with atrial fibrillation - a protocol of a pilot, randomized, double -blind, placebo-controlled study (CANREN-AF trial). Trials. 2020 May 12;21(1):397. doi: 10.1186/s13063-020-04277-3.