Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Atrial Fibrillation, Atrial Flutter

Intervention / Treatment
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* Drug: beta blockers
* Drug: amiodarone
* Drug: ascorbic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Beta Blockers, Ascorbic Acid and Amiodarone | Drug: beta blockers<br>* metoprolol 25mg by mouth every 6 hours<br>* Other names: Toprol XL;Drug: amiodarone<br>* 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<br>* Other names: Cordarone;Drug: ascorbic acid<br>* 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<br>* Other names: vitamin C;|
| Active Comparator: Group B<br>Beta Blockers and Ascorbic Acid | Drug: beta blockers<br>* metoprolol 25mg by mouth every 6 hours<br>* Other names: Toprol XL;Drug: ascorbic acid<br>* 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<br>* Other names: vitamin C;|
| Active Comparator: Group C<br>Beta Blockers and Amiodarone | Drug: beta blockers<br>* metoprolol 25mg by mouth every 6 hours<br>* Other names: Toprol XL;Drug: amiodarone<br>* 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<br>* Other names: Cordarone;|
| Active Comparator: Group D<br>Beta Blockers alone | Drug: beta blockers<br>* metoprolol 25mg by mouth every 6 hours<br>* Other names: Toprol XL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 5 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Mortality | Mortality measured within length of hospital stay | 30 days | 
| Hospital Length of Stay |  | 30 days | 
| ICU Length of Stay |  | 30 days | 
| Number of Participants With Stroke | Cerebral vascular accident occurring within hospital length of stay | 30 days | 
| Number of Participants With Low Output Heart Failure |  | 30 days | 
| Number of Participants With Postoperative Vasoplegia |  | 30 days | 
| Number of Participants With Respiratory Failure Requiring Reintubation |  | 30 days | 
| Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement |  | 30 days | 
| Number of Participants With Acute Kidney Injury | Using the Akin definition | 30 days | 
| Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation |  | 30 days | 
| Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrial fibrillation, cardiac surgery, open heart surgery