- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03536806
Clinical Efficacy of Potassium Canrenoate in Sinus Rhythm Restoration Among Patients With Atrial Fibrillation. (CANREN-AF)
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 Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Rafał Dąbrowski, MD, PhD
- Phone Number: +48 601250732
- Email: rdabrowski45@gmail.com
Study Contact Backup
- Name: Paweł Syska, MD, PhD
- Phone Number: +48 604072667
- Email: psyskamd@gmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
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 Names:
|
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.
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Time Frame: 2 hours.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Time Frame: 2 hours.
|
Atrial fibrillation recurrence within observation period.
Time Frame: Time Frame: 2 hours.
|
Atrial fibrillation recurrence within observation period.
|
Time Frame: 2 hours.
|
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.
|
Time Frame: 24 hours.
|
Safety outcome (exploratory analysis).
Time Frame: Time Frame: 24 hours.
|
hypotension < 90 mm Hg, cardiac conduction abnormalities, new arrhythmia occurrence, other
|
Time Frame: 24 hours.
|
Collaborators and Investigators
Investigators
- Principal Investigator: Rafał Dąbrowski, MD, PhD, Institute of Cardiology
- Study Chair: Tomasz Hryniewiecki, MD, PhD, Institute of Cardiology
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Arrhythmias, Cardiac
- Atrial Fibrillation
- Physiological Effects of Drugs
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Natriuretic Agents
- Diuretics
- Hormone Antagonists
- Mineralocorticoid Receptor Antagonists
- Diuretics, Potassium Sparing
- Canrenone
Other Study ID Numbers
- 2.62/VII/16
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Atrial Fibrillation, Paroxysmal
-
Biosense Webster, Inc.Active, not recruitingRefractory Paroxysmal Atrial FibrillationChina
-
Boston Scientific CorporationCompletedParoxysmal Atrial Fibrillation (PAF)United States, Spain, Germany, Australia, United Kingdom, Sweden, Czechia, France, Portugal
-
Medtronic Cardiac Rhythm and Heart FailureCompletedParoxysmal Atrial Fibrillation (PAF)United States, Canada
-
Hospital Clinic of BarcelonaCompletedDrug-refractory Paroxysmal Atrial FibrillationSpain
-
Biosense Webster, Inc.RecruitingDrug Refractory Paroxysmal Atrial FibrillationUnited States
-
Charite University, Berlin, GermanyGerman Federal Ministry of Education and ResearchTerminatedSymptomatic Paroxysmal Atrial FibrillationGermany
-
Ablacon, Inc.RecruitingAtrial Fibrillation | Arrhythmias, Cardiac | Arrhythmia | Atrial Flutter | Atrial Fibrillation, Persistent | Atrial Tachycardia | Atrial Arrhythmia | Atrial Fibrillation Paroxysmal | Atrial Fibrillation, Paroxysmal or PersistentUnited States, Belgium, Netherlands, Czechia
-
Biosense Webster, Inc.CompletedDrug Refractory Symptomatic Paroxysmal Atrial FibrillationUnited States
-
Medtronic Cardiac Rhythm and Heart FailureMedtronic Atrial Fibrillation SolutionsCompletedSymptomatic Paroxysmal Atrial Fibrillation Without Clinically Significant Heart DiseasesNetherlands, Australia, France, Norway, Germany, Croatia, Italy, Argentina, Belgium
-
Beijing Anzhen HospitalJohnson & Johnson; Heart Health Research CenterNot yet recruitingParoxysmal Atrial Fibrillation | Persistent Atrial Fibrillation
Clinical Trials on Saline 0.9%
-
Tri-Service General HospitalCompleted
-
Vanderbilt University Medical CenterActive, not recruitingPostural Tachycardia SyndromeUnited States
-
University of California, DavisEunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedDiabetic Ketoacidosis | Cerebral EdemaUnited States
-
University of MalayaUnknown
-
Duke UniversityNational Heart, Lung, and Blood Institute (NHLBI)CompletedHeart Diseases | Cardiovascular Diseases | Coronary Disease | Neurologic ManifestationsUnited States
-
Santaris Pharma A/SCompleted
-
Rigshospitalet, DenmarkCompleted
-
Ann & Robert H Lurie Children's Hospital of ChicagoWithdrawn
-
University Hospital Inselspital, BerneCompletedCardiovascular Diseases | Valvular Heart DiseaseSwitzerland
-
CSL BehringTerminatedOral MucositisUnited States, Canada, Australia, Germany, Italy, Austria