Carvedilol for Prevention of Paroxysmal Atrial Fibrillation

NCT ID: NCT01608893

Last Updated: 2022-05-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2025-06-30

Brief Summary

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder and is associated with significant symptoms and health problems including an increased risk of stroke and death. Current drug therapies are often ineffective and associated with significant side effects. Abnormalities of calcium regulation in cells may lead to triggers for AF. Emerging data suggest that abnormal intracellular calcium regulation mediated through the ryanodine receptor in heart cells may contribute to AF. Recently the investigators have shown that the β-blocker carvedilol which is most commonly used to treat patients with heart failure, modifies calcium regulation mediated through the ryanodine receptor. At present this drug is not frequently used to treat AF. Therefore the investigators will conduct a randomized trial comparing carvedilol to metoprolol for prevention of paroxysmal AF. This may result in improved health and quality of life for people who suffer AF.

Detailed Description

The study population will consist of patients with electrocardiographically documented symptomatic paroxysmal AF (≥ 2 episodes of ≥ 15 min duration within a six month period) while on stable antiarrhythmic drug therapy. Patients will be excluded if they have AF due to a reversible cause, persistent AF, significant heart failure or a life expectancy of less than one year. Eligible patients will be randomized to carvedilol or metoprolol and followed for 13 months. Randomization will be stratified based on the AF management strategy (rate or rhythm control). Carvedilol and metoprolol will be initiated over a one month drug titration period to achieve doses of 25mg bid and 50 mg bid respectively. AF occurrence will be documented using event recorders. The co-primary outcome measures are survival free from AF after one month blanking period for drug titration and the number of days in AF detected during follow-up. Secondary outcomes include event free survival to first symptomatic episode of AF, days in symptomatic AF, time between first and second episodes of AF, proportion of patients who develop persistent AF, AF Severity Scale, CCS-AF symptom score, ventricular rate during AF, proportion of patients with discontinuation of the assigned therapy and number of emergency department visits or hospitalizations for cardiovascular causes. Adverse effects and need to discontinue carvedilol or metoprolol will be documented. This study will determine whether carvedilol is safe and effective for prevention of recurrent paroxysmal AF in a general population with AF. Data will be analyzed on an intention to treat basis. Three hundred patients will be recruited over 4 years. The sample size is based on an estimated 20% reduction in event free survival from AF (power 0.90, α = 0.05). Patients will be recruited from our AF clinic population which averages 50 new referrals per month and over 2500 referrals since it's' inception in 2005.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Metoprolol

The metoprolol arm patients are stratified by the arrhythmia management strategy Rate or Rhythm control and metoprolol is dose titrated from 25 mg bid to a maximum of 50 mg bid over one month then patients are followed for 6 months.

Group Type: ACTIVE_COMPARATOR

Metoprolol

Intervention Type: DRUG

titrated to 50 mg po bid as tolerated over a 1 month period

Carvedilol

The carvedilol arm patients are stratified by the arrhythmia management strategy Rate or Rhythm control and carvedilol is dose titrated from 3.25 mg bid to maximum dose of 25 mg bid over one month then patients are followed for 6 months.

Group Type: ACTIVE_COMPARATOR

Carvedilol

Intervention Type: DRUG

6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period

Interventions

Carvedilol

6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period

Intervention Type: DRUG

Metoprolol

titrated to 50 mg po bid as tolerated over a 1 month period

Intervention Type: DRUG

Other Intervention Names

Coreg; Lopressor

Eligibility Criteria

Inclusion Criteria

• Must be in sinus rhythm at enrollment
• ECG documented symptomatic PAF (> 2 episodes of > 15minutes duration over a 6 month period)

Exclusion Criteria

• AF due to reversible causes
• Contraindication or previous significant adverse reaction to Beta blocker therapy
• Persistent AF
• NYHA Class II or greater CHF
• LVEF < or = 35%
• Life expectancy < 1 year
• Geographic isolation
• Unable to give informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Heart and Stroke Foundation of Canada

OTHER

Sponsor Role: collaborator

Libin Cardiovascular Institute of Alberta

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Dr. Anne M. Gillis

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anne M Gillis, M.D.

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine

Locations

University of Calgary

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

Carvedilol for PAF

Identifier Type: -

Identifier Source: org_study_id