Carvedilol for Prevention of Paroxysmal Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

Carvedilol for Prevention of Paroxysmal Atrial Fibrillation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01608893
• Other study ID #: Carvedilol for PAF
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 2012
• Est. completion date: June 2025

Study information

• Verified date: May 2022
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Carvedilol
6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period
• Metoprolol
titrated to 50 mg po bid as tolerated over a 1 month period

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta

Sponsors (3)

Lead Sponsor	Collaborator
University of Calgary	Heart and Stroke Foundation of Canada, Libin Cardiovascular Institute of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival to first detected AF after the one month blanking period for dose titration	Time to first AF detected by event recorder transmission will be determined.	1 year
Secondary	number of Emergency room visits/hospitalizations for cardiovascular causes	Subjects will be questioned via telephone interview or clinic visit every 3 months and appropriate hospital recorders retrieved for confirmation of event.	1 year
Secondary	Proportion of patients who develop persistent AF		1 year
Secondary	Days in symptomatic AF/Time between successive PAF episodes	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.	1 year
Secondary	AF Severity Scale	Measured via University of Toronto AF Severity Scale at baseline and at end of study or study exit	1 year
Secondary	Adverse effects of assigned therapy	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.	1 year
Secondary	Ventricular rate during AF	Ventricular rate during AF will be measured from the event recorder tracings - from 10 sec of recording	1 year
Secondary	CCS AF Symptom Score	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.	1 yr