A Phase 3 interventional study of beta blockers and amiodarone in Atrial Fibrillation and Atrial Flutter, sponsored by MaineHealth. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-04-26.
Sponsored by MaineHealth · Phase 3, Interventional, and Prevention
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.
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.
3,870 studies on the registry are indexed under Atrial Fibrillation; 924 are open to participants now.
This study's enrollment of 304 is above the median of 144 across 2,380 interventional studies indexed under Atrial Fibrillation.
Browse Atrial Fibrillation studies →MaineHealth is the lead sponsor of 34 studies on the registry; 5 are open to participants now.
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Exclusion Criteria:
Beta Blockers, Ascorbic Acid and Amiodarone
Drug: beta blockers · Drug: amiodarone · Drug: ascorbic acid
Beta Blockers and Ascorbic Acid
Drug: beta blockers · Drug: ascorbic acid
Beta Blockers and Amiodarone
Drug: beta blockers · Drug: amiodarone
Beta Blockers alone
Drug: beta blockers
metoprolol 25mg by mouth every 6 hours
Also known as: Lopressor, Toprol XL
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
Also known as: Cordarone
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
Also known as: vitamin C
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.
Time frame: 5 postoperative days
Number of Participants With Mortality
Mortality measured within length of hospital stay
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
Cerebral vascular accident occurring within hospital length of stay
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
Using the Akin definition
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
| Milestone | Beta Blockers, Ascorbic Acid and Amiodarone | Beta Blockers and Ascorbic Acid | Beta Blockers and Amiodarone | Beta Blockers Alone |
|---|---|---|---|---|
| Started | 76 | 74 | 78 | 76 |
| Completed | 76 | 74 | 78 | 76 |
| Not completed | 0 | 0 | 0 | 0 |
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.
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery | 50 | 56 | 58 | 48 |
Mortality measured within length of hospital stay
| Participants | Beta Blockers, Ascorbic Acid and Amiodarone | Beta Blockers and Ascorbic Acid | Beta Blockers and Amiodarone | Beta Blockers Alone |
|---|---|---|---|---|
| Number of Participants With Mortality | 1 | 1 | 1 | 0 |
| days | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Hospital Length of Stay | 7.0 ± 4.8 | 6.6 ± 3.8 | 6.8 ± 3.6 | 6.8 ± 4.9 |
| days | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| ICU Length of Stay | 2.0 ± 1.5 | 1.9 ± 1.3 | 2.0 ± 1.3 | 1.9 ± 1.5 |
Cerebral vascular accident occurring within hospital length of stay
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Stroke | 1 | 3 | 1 | 1 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Low Output Heart Failure | 12 | 10 | 7 | 9 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Postoperative Vasoplegia | 17 | 15 | 14 | 16 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Respiratory Failure Requiring Reintubation | 4 | 2 | 2 | 5 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement | 0 | 2 | 0 | 2 |
Using the Akin definition
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Acute Kidney Injury | 19 | 13 | 22 | 11 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation | 1 | 1 | 2 | 0 |
| Participants | Amiodarone - Yes | Amiodarone - No | Ascorbic Acid - Yes | Ascorbic Acid - No |
|---|---|---|---|---|
| Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation | 4 | 4 | 4 | 4 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A | 1/76 (1.3%) | 1/76 (1.3%) | 29/76 (38.2%) |
| Group B | 1/74 (1.4%) | 3/74 (4.1%) | 29/74 (39.2%) |
| Group C | 1/78 (1.3%) | 1/78 (1.3%) | 21/78 (26.9%) |
| Group D | 0/76 (0%) | 1/76 (1.3%) | 27/76 (35.5%) |
| Event | Group A | Group B | Group C | Group D |
|---|---|---|---|---|
| Cerebral Vascular AccidentNervous system disorders | 1/76 | 3/74 | 1/78 | 1/76 |
| Event | Group A | Group B | Group C | Group D |
|---|---|---|---|---|
| Atrial fibrillationCardiac disorders | 29/76 | 29/74 | 21/78 | 27/76 |
| Age, Continuous(years) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Mean | 64.3 ± 9.6 | 65.9 ± 9.4 | 63.9 ± 10.7 | 33.4 ± 931 | 61 ± 15 |
| Sex: Female, Male(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Female | 16 | 19 | 19 | 20 | 74 |
| Male | 60 | 55 | 59 | 56 | 230 |
| Race (NIH/OMB)(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 1 | 1 |
| White | 76 | 74 | 77 | 75 | 302 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 1 | 0 | 1 |
| Smoker(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Count of participants | 16 | 19 | 21 | 19 | 75 |
| BMI (mean, SD)(kg/m^2) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Mean | 30.6 ± 6.1 | 31.1 ± 5.7 | 27.9 ± 4.7 | 29.5 ± 6.2 | 29.7 ± 5.8 |
| Cardiovascular Disease(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Count of participants | 11 | 13 | 14 | 13 | 51 |
| Hypertension(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Count of participants | 69 | 63 | 62 | 65 | 259 |
| Pre-op Myocardial Infarction(Participants) | Group A | Group B | Group C | Group D | Total |
|---|---|---|---|---|---|
| Count of participants | 24 | 30 | 29 | 35 | 118 |
10 further baseline measures are reported on the registry.
This study is completed, as verified in Mar 2018. You cannot join it, but the record below documents what was studied.
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