Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation.

Atrial Fibrillation, Paroxysmal Clinical Trial

— CANREN-AF  

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03536806
• Other study ID #: 2.62/VII/16
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 2018
• Est. completion date: December 2020

Study information

• Verified date: May 2018
• Source: Institute of Cardiology, Warsaw, Poland
• Contact: Rafal Dabrowski, MD, PhD
• Phone: +48 601250732
• Email: rdabrowski45[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation, Paroxysmal

Intervention

Drug:
• Saline 0.9%
Patients assigned to control group will be administered saline 0.9% in bolus of 10 cm3 within 2-3 minutes. BP will be measured before injection.
• Canrenone
Patients assigned to canrenone group will be administered canrenone in bolus of 200 mg diluted to 10 cm3 within 2-3 minutes in one dose. Drug administration will be stopped in case of serious adverse event. Further treatment of the patient will depend on clinical condition and will follow appropriate clinical guidelines.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Cardiology, Warsaw, Poland

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Conversion of atrial fibrillation to sinus rhythm.	Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.	Time Frame: 2 hours.
Secondary	Time to conversion of atrial fibrillation to sinus rhythm.	Time to conversion of atrial fibrillation to sinus rhythm in minutes since injection.	Time Frame: 2 hours.
Secondary	Atrial fibrillation recurrence within observation period.	Atrial fibrillation recurrence within observation period.	Time Frame: 2 hours.
Secondary	Serious adverse reactions.	Serious adverse reactions, which refer to every event requiring admission to a hospital or extended observation.	Time Frame: 24 hours.
Secondary	Safety outcome (exploratory analysis).	hypotension < 90 mm Hg, cardiac conduction abnormalities, new arrhythmia occurrence, other	Time Frame: 24 hours.