Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation. (CANREN-AF)

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ClinicalTrials.gov Identifier: NCT03536806

Recruitment Status : Not yet recruiting

First Posted : May 25, 2018

Last Update Posted : May 25, 2018

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Sponsor:

Information provided by (Responsible Party):

Rafał Dąbrowski, Institute of Cardiology, Warsaw, Poland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation, Paroxysmal	Drug: Saline 0.9% Drug: Canrenone	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Parallel Assignment
Masking:	Double (Participant, Care Provider)
Masking Description:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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.
Estimated Study Start Date :	June 2018
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2020

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Familial atrial fibrillation Hypertension

MedlinePlus related topics: Atrial Fibrillation Potassium

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 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.	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. Other Name: saline 0.9% in bolus of 10 cm3
Experimental: 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.	Drug: 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. Other Name: canrenone in bolus of 200 mg diluted to 10 cm3

Arm

Intervention/treatment

Placebo Comparator: 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.

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.

Other Name: saline 0.9% in bolus of 10 cm3

Experimental: 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.

Drug: 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.

Other Name: canrenone in bolus of 200 mg diluted to 10 cm3

Outcome Measures

Primary Outcome Measures :

Conversion of atrial fibrillation to sinus rhythm. [ Time Frame: Time Frame: 2 hours. ]
Conversion of atrial fibrillation to sinus rhythm confirmed in standard 12-lead ECG during observation period after first iv bolus.

Secondary Outcome Measures :

Time to conversion of atrial fibrillation to sinus rhythm. [ Time Frame: Time Frame: 2 hours. ]
Time to conversion of atrial fibrillation to sinus rhythm in minutes since injection.
Atrial fibrillation recurrence within observation period. [ Time Frame: Time Frame: 2 hours. ]
Atrial fibrillation recurrence within observation period.
Serious adverse reactions. [ Time Frame: Time Frame: 24 hours. ]
Serious adverse reactions, which refer to every event requiring admission to a hospital or extended observation.
Safety outcome (exploratory analysis). [ Time Frame: Time Frame: 24 hours. ]
hypotension < 90 mm Hg, cardiac conduction abnormalities, new arrhythmia occurrence, other

Eligibility Criteria

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Ages Eligible for Study:	40 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03536806

Contacts

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Contact: Rafał Dąbrowski, MD, PhD	+48 601250732	rdabrowski45@gmail.com
Contact: Paweł Syska, MD, PhD	+48 604072667	psyskamd@gmail.com

Sponsors and Collaborators

Institute of Cardiology, Warsaw, Poland

Investigators

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Principal Investigator:	Rafał Dąbrowski, MD, PhD	Institute of Cardiology
Study Chair:	Tomasz Hryniewiecki, MD, PhD	Institute of Cardiology

More Information

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Responsible Party:	Rafał Dąbrowski, Rafal Dabrowski, MD, PhD, Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier:	NCT03536806 History of Changes
Other Study ID Numbers:	2.62/VII/16
First Posted:	May 25, 2018 Key Record Dates
Last Update Posted:	May 25, 2018
Last Verified:	May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Rafał Dąbrowski, Institute of Cardiology, Warsaw, Poland:


Pharmacological cardioversion Canrenone

Additional relevant MeSH terms:

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Atrial Fibrillation Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Canrenone Canrenoic Acid	Mineralocorticoid Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents

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