Carvedilol for Prevention of Paroxysmal Atrial Fibrillation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Heart and Stroke Foundation of Canada
Libin Cardiovascular Institute of Alberta
Information provided by (Responsible Party):
Dr. Anne M. Gillis, University of Calgary
ClinicalTrials.gov Identifier:
NCT01608893
First received: May 28, 2012
Last updated: May 30, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
Atrial Fibrillation
Drug: Carvedilol
Drug: Metoprolol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Carvedilol for Prevention of Paroxysmal Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Event-free survival to first detected AF after the one month blanking period for dose titration [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Time to first AF detected by event recorder transmission will be determined.

  • Days in Detected AF [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The number of days in which AF was detected by event recorder transmisions will be documented


Secondary Outcome Measures:
  • number of Emergency room visits/hospitalizations for cardiovascular causes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Subjects will be questioned via telephone interview or clinic visit every 3 months and appropriate hospital recorders retrieved for confirmation of event.

  • Proportion of patients who develop persistent AF [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Days in symptomatic AF/Time between successive PAF episodes [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The days in which patients report symptomatic AF confirmed by event recorder transmission will be determined and the time interval between successive events will be determined.

  • AF Severity Scale [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Measured via University of Toronto AF Severity Scale at baseline and at end of study or study exit

  • Adverse effects of assigned therapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Adverse effects thought to be related to drug therapy will be documented as well as number of patients in whom drug is discontined because of adverse events.

  • Ventricular rate during AF [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Ventricular rate during AF will be measured from the event recorder tracings - from 10 sec of recording

  • CCS AF Symptom Score [ Time Frame: 1 yr ] [ Designated as safety issue: No ]

    This will be determined from interview at baseline and each follow-up visit. The CCS AF symptom score is a 5 point score from 0 to 4.

    CCS-SAF Class Definitions

    Class 0 Asymptomatic with respect to AF Class 1 Symptoms attributable to AF have minimal effect on patient's general QOL.

    Class 2 Symptoms attributable to AF have a minor effect on patient's general QOL.

    Class 3 Symptoms attributable to AF have a moderate effect on patient's general QOL.

    Class 4 Symptoms attributable to AF have a severe effect on patient's general QOL.



Estimated Enrollment: 300
Study Start Date: May 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metoprolol Drug: Metoprolol
titrated to 50 mg po bid as tolerated over a 1 month period
Other Name: Lopressor
Active Comparator: Carvedilol Drug: Carvedilol
6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period
Other Name: Coreg

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01608893

Locations
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Sponsors and Collaborators
University of Calgary
Heart and Stroke Foundation of Canada
Libin Cardiovascular Institute of Alberta
Investigators
Principal Investigator: Anne M Gillis, M.D. Professor of Medicine
  More Information

No publications provided

Responsible Party: Dr. Anne M. Gillis, Professor of Medicine, University of Calgary
ClinicalTrials.gov Identifier: NCT01608893     History of Changes
Other Study ID Numbers: Carvedilol for PAF
Study First Received: May 28, 2012
Last Updated: May 30, 2012
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Metoprolol
Carvedilol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists

ClinicalTrials.gov processed this record on July 28, 2014