Atrial FibrillationNCT01608893
Carvedilol for Prevention of Paroxysmal Atrial Fibrillation
A study testing Carvedilol and Metoprolol in people with Atrial Fibrillation, run by University of Calgary at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Carvedilol and Metoprolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteCanada
- Study dates
- May 2012to Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Must be in sinus rhythm at enrollment
- ECG documented symptomatic PAF (> 2 episodes of > 15minutes duration over a 6 month period)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Carvedilol, Metoprolol
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Also called Coreg
6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period
MetoprololDrug
Also called Lopressor
titrated to 50 mg po bid as tolerated over a 1 month period
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol | Active comparator | 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. Receives: Drug: Metoprolol |
| Carvedilol | Active comparator | 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. Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (7)
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.
Measured: 1 year
Proportion of patients who develop persistent AF
Measured: 1 year
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.
Measured: 1 year
AF Severity Scale
Measured via University of Toronto AF Severity Scale at baseline and at end of study or study exit
Measured: 1 year
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.
Measured: 1 year
Ventricular rate during AF
Ventricular rate during AF will be measured from the event recorder tracings - from 10 sec of recording
Measured: 1 year
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.
Measured: 1 yr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study startMay 2012
- Primary completionJun 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Canada, Libin Cardiovascular Institute of Alberta
- Responsible party
- Principal investigator, Dr. Anne M. Gillis, University of Calgary
- Investigators
- Anne M Gillis, M.D., Principal investigator, Professor of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01608893
- Sponsor's protocol ID
- Carvedilol for PAF
- Status last verified
- May 2022
- First submitted
- 28 May 2012
- Last updated
- 27 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carvedilol for Prevention of Paroxysmal Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT01608893
- Acronym / sponsor ID
- Carvedilol for PAF
- Conditions
- Atrial Fibrillation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Canada, Libin Cardiovascular Institute of Alberta
- Study start
- May 2012 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 31 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol | Active comparator | Drug: MetoprololThe 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. |
| Carvedilol | Active comparator | Drug: CarvedilolThe 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Must be in sinus rhythm at enrollment
- ECG documented symptomatic PAF (> 2 episodes of > 15minutes duration over a 6 month period)
Key exclusion criteria (8 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolAlso: Coreg6.25 po bid titrated to 25 mg bid as tolerated over a 1 month period | Drug | Carvedilol |
| MetoprololAlso: Lopressortitrated to 50 mg po bid as tolerated over a 1 month period | Drug | Metoprolol |
Primary outcome
Event-free survival to first detected AF after the one month blanking period for dose titration
Time frame: 1 year
Time to first AF detected by event recorder transmission will be determined.
7 secondary outcomes
number of Emergency room visits/hospitalizations for cardiovascular causes
Time frame: 1 year
Proportion of patients who develop persistent AF
Time frame: 1 year
Days in symptomatic AF/Time between successive PAF episodes
Time frame: 1 year
AF Severity Scale
Time frame: 1 year
Adverse effects of assigned therapy
Time frame: 1 year
Ventricular rate during AF
Time frame: 1 year
CCS AF Symptom Score
Time frame: 1 yr
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne M Gillis, M.D. principal investigator
Professor of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carvedilol and Metoprolol in people with Atrial Fibrillation, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival to first detected AF after the one month blanking period for dose titration (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2022.