Atrial FibrillationPhase 3NCT00953212
Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery
A Phase 3 study testing beta blockers, amiodarone and ascorbic acid in people with Atrial Fibrillation and Atrial Flutter, run by MaineHealth at 1 site in United States.
Trial summary
Atrial Fibrillation (AF) is a common postoperative complication of cardiac surgery, occuring in approximately 25-30% of coronary artery bypass graft (CABG) patients and 35-40% of heart valve repair/replacement patients. Efforts to decrease the high rates of AF have not made great inroads to the problem. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Atrial Flutter
- What is being tested?
- beta blockers, amiodarone and ascorbic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Feb 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adults (18 years of age or older)
- all comers for elective or urgent open heart surgery ( CABG, Valve repair or replacement, Combined CABG/Valves, CABG/other, Other)
Who cannot join
- patients who refuse to participate
- patients with a history of atrial fibrillation or atrial flutter
- pediatric patients (under 18 years of age)
- Emergency surgery
- patients with contraindications to study medications
- patients with untreated thyroid disease, hepatic failure, pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial to Compare Prophylaxis With Oral Ascorbic Acid, Oral Amiodarone or Both in Combination With Beta Blockers to Reduce Postoperative Atrial Fibrillation After Cardiac Surgery
Atrial Fibrillation (AF) is a common postoperative complication of cardiac surgery, occuring in approximately 25-30% of coronary artery bypass graft (CABG) patients and 35-40% of heart valve repair/replacement patients. Efforts to decrease the high rates of AF have not made great inroads to the problem. The current standard of care is the use of preoperative and postoperative beta blockers. We propose to compare the use of prophylactic oral ascorbic acid with and without prophylactic oral amiodarone, in combination with oral beta blockers, for the prevention of atrial fibrillation after open heart surgery. The hypothesis is that either drug, or a combination of the two drugs, will be superior and safe when compared to beta blockers alone.
Read the detailed description
Atrial fibrillation is a common complication of cardiac surgery which is associated with increased morbidity, length of stay and cost. Efforts to mitigate this problem with beta blockers and amiodarone have been met with limited success. Observational data suggests that prophylactic amiodarone has been helpful in decreasing the incidence of AF as well as increasing its ease of management. The opportunity to use ascorbic acid for AF prophylaxis is attractive because of its low side effect profile, wide acceptance and low cost.
We have designed a prospective, randomized, controlled trial using a 2 X 2 factorial design to determine whether prophylactic ascorbic acid alone, ascorbic acid with amiodarone, or amiodarone alone, when given along with beta blockers will decrease the incidence of postoperative AF in adult cardiac surgery in all comers as compared with beta blockers alone.
Patients will be randomized into four groups, A, B, C, and D. All groups will receive beta blockers, Group A will receive beta blockers, ascorbic acid, and amiodarone, Group B will receive ascorbic acid and Beta blockers, Group C will receive amiodarone and beta blockers and Group D will receive only beta blockers.
Success of randomization will be assessed by comparing treatment groups with respect to baseline characteristics, using t-tests or their nonparametric equivalent (as appropriate) for continuous variables and chisquare tests or Fisher's exact tests for categorical variables. The primary hypotheses of the effects of ascorbic acid and amiodarone on incidence of atrial fibrillation will be tested using chisquare tests for differences in proportions. No adjustment will be made for multiple comparisons since both hypotheses are pre-specified. We will use exploratory analyses including stratification to assess for the possibility of effect modification between ascorbic acid and amiodarone. If an interaction is suggested by these analyses, we will use logistic regression with a cross-product term as a formal statistical test for interaction.
- Conditions
- Atrial Fibrillation, Atrial Flutter
- Being tested
- beta blockers, amiodarone, ascorbic acid
- Keywords
- atrial fibrillation, cardiac surgery, open heart surgery
- Medical subject headings
- Atrial Fibrillation, Atrial Flutter
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beta blockersDrug
Also called Lopressor, Toprol XL
metoprolol 25mg by mouth every 6 hours
amiodaroneDrug
Also called Cordarone
amiodarone 600mg by mouth evening before surgery amiodarone 600mg by mouth morning of surgery amiodarone 400mg by mouth every 12 hours for 3 days postoperatively
ascorbic acidDrug
Also called vitamin C
ascorbic acid 2,000mg by mouth evening before surgery ascorbic acid 2,000mg by mouth morning of surgery ascorbic acid 1,000mg by mouth every 12 hours for 5 postoperative days
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Beta Blockers, Ascorbic Acid and Amiodarone Receives: Drug: beta blockers; Drug: amiodarone; Drug: ascorbic acid |
| Group B | Active comparator | Beta Blockers and Ascorbic Acid Receives: Drug: beta blockers; Drug: ascorbic acid |
| Group C | Active comparator | Beta Blockers and Amiodarone Receives: Drug: beta blockers; Drug: amiodarone |
| Group D | Active comparator | Beta Blockers alone Receives: Drug: beta blockers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery
Atrial fibrillation is a common complication of cardiac surgery which is associated with increased morbidity, length of stay and cost. The opportunity to use ascorbic acid for AF prophylaxis is attractive because of its low side effect profile, wide acceptance and low cost. This prospective, randomized trial used a 2 X 2 factorial design to determine whether prophylactic ascorbic acid alone, ascorbic acid with amiodarone, or amiodarone alone, when given along with beta blockers would decrease the incidence of postoperative AF in adult cardiac surgery when compared with beta blockers alone, all combinations failed to show any difference between the four groups. While there have been trials that have shown the addition of amiodarone to beta-blockers to be more effective, this analysis does not support that conclusion.
Measured: 5 postoperative days
Secondary outcomes (11)
Number of Participants With Mortality
Mortality measured within length of hospital stay
Measured: 30 days
Hospital Length of Stay
Measured: 30 days
ICU Length of Stay
Measured: 30 days
Number of Participants With Stroke
Cerebral vascular accident occurring within hospital length of stay
Measured: 30 days
Number of Participants With Low Output Heart Failure
Measured: 30 days
Number of Participants With Postoperative Vasoplegia
Measured: 30 days
Number of Participants With Respiratory Failure Requiring Reintubation
Measured: 30 days
Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement
Measured: 30 days
Number of Participants With Acute Kidney Injury
Using the Akin definition
Measured: 30 days
Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation
Measured: 30 days
Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- MaineHealth
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter C. Donovan, MaineHealth
- Investigators
- Peter C Donovan, PA-C, MHS, Principal investigator, MaineHealthRobert S Kramer, M.D., Study chair, MaineHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00953212
- Sponsor's protocol ID
- MMC-3514
- Status last verified
- Mar 2018
- First submitted
- 5 Aug 2009
- Last updated
- 26 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial to Compare Prophylaxis With Oral Ascorbic Acid, Oral Amiodarone or Both in Combination With Beta Blockers to Reduce Postoperative Atrial Fibrillation After Cardiac Surgery
- ClinicalTrials.gov ID
- NCT00953212
- Acronym / sponsor ID
- MMC-3514
- Conditions
- Atrial Fibrillation, Atrial Flutter
- Keywords
- atrial fibrillation, cardiac surgery, open heart surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- MaineHealthUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Jan 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 6 Aug 2009 (estimated)
- Results
- Posted 29 Mar 2018
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 a common postoperative complication of cardiac surgery, occuring in approximately 25-30% of coronary artery bypass graft (CABG) patients and 35-40% of heart valve repair/replacement patients. Efforts to decrease the high rates of AF have not made great inroads to the problem. The current standard of care is the use of preoperative and postoperative beta blockers. We propose to compare the use of prophylactic oral ascorbic acid with and without prophylactic oral amiodarone, in combination with oral beta blockers, for the prevention of atrial fibrillation after open heart surgery. The hypothesis is that either drug, or a combination of the two drugs, will be superior and safe when compared to beta blockers alone.
Detailed description
Atrial fibrillation is a common complication of cardiac surgery which is associated with increased morbidity, length of stay and cost. Efforts to mitigate this problem with beta blockers and amiodarone have been met with limited success. Observational data suggests that prophylactic amiodarone has been helpful in decreasing the incidence of AF as well as increasing its ease of management. The opportunity to use ascorbic acid for AF prophylaxis is attractive because of its low side effect profile, wide acceptance and low cost.
We have designed a prospective, randomized, controlled trial using a 2 X 2 factorial design to determine whether prophylactic ascorbic acid alone, ascorbic acid with amiodarone, or amiodarone alone, when given along with beta blockers will decrease the incidence of postoperative AF in adult cardiac surgery in all comers as compared with beta blockers alone.
Patients will be randomized into four groups, A, B, C, and D. All groups will receive beta blockers, Group A will receive beta blockers, ascorbic acid, and amiodarone, Group B will receive ascorbic acid and Beta blockers, Group C will receive amiodarone and beta blockers and Group D will receive only beta blockers.
Success of randomization will be assessed by comparing treatment groups with respect to baseline characteristics, using t-tests or their nonparametric equivalent (as appropriate) for continuous variables and chisquare tests or Fisher's exact tests for categorical variables. The primary hypotheses of the effects of ascorbic acid and amiodarone on incidence of atrial fibrillation will be tested using chisquare tests for differences in proportions. No adjustment will be made for multiple comparisons since both hypotheses are pre-specified. We will use exploratory analyses including stratification to assess for the possibility of effect modification between ascorbic acid and amiodarone. If an interaction is suggested by these analyses, we will use logistic regression with a cross-product term as a formal statistical test for interaction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: beta blockers, Drug: amiodarone, Drug: ascorbic acidBeta Blockers, Ascorbic Acid and Amiodarone |
| Group B | Active comparator | Drug: beta blockers, Drug: ascorbic acidBeta Blockers and Ascorbic Acid |
| Group C | Active comparator | Drug: beta blockers, Drug: amiodaroneBeta Blockers and Amiodarone |
| Group D | Active comparator | Drug: beta blockersBeta Blockers alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- adults (18 years of age or older)
- all comers for elective or urgent open heart surgery ( CABG, Valve repair or replacement, Combined CABG/Valves, CABG/other, Other)
Key exclusion criteria (6 listed)
- patients who refuse to participate
- patients with a history of atrial fibrillation or atrial flutter
- pediatric patients (under 18 years of age)
- Emergency surgery
- patients with contraindications to study medications
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 |
|---|---|---|
| beta blockersAlso: Lopressor, Toprol XLmetoprolol 25mg by mouth every 6 hours | Drug | Group A, Group B, Group C, Group D |
| amiodaroneAlso: Cordaroneamiodarone 600mg by mouth evening before surgery amiodarone 600mg by mouth morning of surgery amiodarone 400mg by mouth every 12 hours for 3 days postoperatively | Drug | Group A, Group C |
| ascorbic acidAlso: vitamin Cascorbic acid 2,000mg by mouth evening before surgery ascorbic acid 2,000mg by mouth morning of surgery ascorbic acid 1,000mg by mouth every 12 hours for 5 postoperative days | Drug | Group A, Group B |
Primary outcome
Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery
Time frame: 5 postoperative days
Atrial fibrillation is a common complication of cardiac surgery which is associated with increased morbidity, length of stay and cost. The opportunity to use ascorbic acid for AF prophylaxis is attractive because of its low side effect profile, wide acceptance and low cost. This prospective, randomized trial used a 2 X 2 factorial design to determine whether prophylactic ascorbic acid alone, ascorbic acid with amiodarone, or amiodarone alone, when given along with beta blockers would decrease the incidence of postoperative AF in adult cardiac surgery when compared with beta blockers alone, all combinations failed to show any difference between the four groups. While there have been trials that have shown the addition of amiodarone to beta-blockers to be more effective, this analysis does not support that conclusion.
11 secondary outcomes
Number of Participants With Mortality
Time frame: 30 days
Hospital Length of Stay
Time frame: 30 days
ICU Length of Stay
Time frame: 30 days
Number of Participants With Stroke
Time frame: 30 days
Number of Participants With Low Output Heart Failure
Time frame: 30 days
Number of Participants With Postoperative Vasoplegia
Time frame: 30 days
Number of Participants With Respiratory Failure Requiring Reintubation
Time frame: 30 days
Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement
Time frame: 30 days
Number of Participants With Acute Kidney Injury
Time frame: 30 days
Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation
Time frame: 30 days
Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Atrial Fibrillation
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Paroxysmal AF
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Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
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CONVERGE Post-Approval Study (PAS)
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RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
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.
Peter C Donovan, PA-C, MHS principal investigator
MaineHealth
Robert S Kramer, M.D. study chair
MaineHealth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing beta blockers, amiodarone and ascorbic acid in people with Atrial Fibrillation and Atrial Flutter, run by MaineHealth at 1 site in United States.
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 6 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: finished, as of the sponsor's last update on 26 Apr 2018. 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 United States. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery (time frame: 5 postoperative days). 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 26 Apr 2018.