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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Active Comparator | Beta Blockers, Ascorbic Acid and Amiodarone |
|
| Group B | Active Comparator | Beta Blockers and Ascorbic Acid |
|
| Group C | Active Comparator | Beta Blockers and Amiodarone |
|
| Group D | Active Comparator | Beta Blockers alone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| beta blockers | Drug | metoprolol 25mg by mouth every 6 hours |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Mortality | Mortality measured within length of hospital stay | 30 days |
| Hospital Length of Stay | 30 days | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter C Donovan, PA-C, MHS | MaineHealth | Principal Investigator |
| Robert S Kramer, M.D. | MaineHealth | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maine Medical Center | Portland | Maine | 04102 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Beta Blockers, Ascorbic Acid and Amiodarone | beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 acid: 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 |
| FG001 | Beta Blockers and Ascorbic Acid | Beta Blockers and Ascorbic Acid beta blockers: metoprolol 25mg by mouth every 6 hours ascorbic acid: 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 |
| FG002 | Beta Blockers and Amiodarone | Beta Blockers and Amiodarone beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 |
| FG003 | Beta Blockers Alone | Beta Blockers alone beta blockers: metoprolol 25mg by mouth every 6 hours |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A | Beta Blockers, Ascorbic Acid and Amiodarone beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 acid: 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Number of patients who experienced Atrial Fibrillation post-operatively | Posted | Count of Participants | Participants | 5 postoperative days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A | Beta Blockers, Ascorbic Acid and Amiodarone beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 acid: 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebral Vascular Accident | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert Kramer | Maine Medical Center | 207-662-2923 | KRAMER@mmc.org |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D001282 | Atrial Flutter |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000319 | Adrenergic beta-Antagonists |
| D008790 | Metoprolol |
| D000638 | Amiodarone |
| D001205 | Ascorbic Acid |
| ID | Term |
|---|---|
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
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| amiodarone | Drug | 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 acid | Drug | 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 |
|
|
| 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 |
| BG001 | Group B | Beta Blockers and Ascorbic Acid beta blockers: metoprolol 25mg by mouth every 6 hours ascorbic acid: 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 |
| BG002 | Group C | Beta Blockers and Amiodarone beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 |
| BG003 | Group D | Beta Blockers alone beta blockers: metoprolol 25mg by mouth every 6 hours |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Smoker | Count of Participants | Participants |
|
| BMI (mean, SD) | Mean | Standard Deviation | kg/m^2 |
|
| Cardiovascular Disease | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Pre-op Myocardial Infarction | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| Peripheral Vascular Disease | Count of Participants | Participants |
|
| Chronic Obstructive Pulmonary Disease | Count of Participants | Participants |
|
| Statin | Count of Participants | Participants |
|
| Congestive Heart Failure | Count of Participants | Participants |
|
| Surgery Type - CABG | Count of Participants | Participants |
|
| Surgery Type - Valve | Count of Participants | Participants |
|
| Surgery Type - CABG/Valve | Count of Participants | Participants |
|
| Surgery Type - Other | Other surgeries include ascending aortic repair, myxoma excision, patent ductus foramen ovale closure, or endarterectomy | Count of Participants | Participants |
|
| Urgent Surgery | Count of Participants | Participants |
|
| OG000 |
| Amiodarone - Yes |
Patients who were administered Amiodarone and Beta Blockers with or without Ascorbic Acid. |
| OG001 | Amiodarone - No | Patients who were not administered Amiodarone and Beta Blockers with or without Ascorbic Acid. |
| OG002 | Ascorbic Acid - Yes | Patients who were administered Ascorbic Acid and Beta Blockers with or without Amiodarone. |
| OG003 | Ascorbic Acid - No | Patients who were not administered Ascorbic Acid and Beta Blockers with or without Amiodarone. |
|
|
| Secondary | Number of Participants With Mortality | Mortality measured within length of hospital stay | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Hospital Length of Stay | Posted | Mean | Standard Deviation | days | 30 days |
|
|
|
| Secondary | ICU Length of Stay | Posted | Mean | Standard Deviation | days | 30 days |
|
|
|
| Secondary | Number of Participants With Stroke | Cerebral vascular accident occurring within hospital length of stay | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Low Output Heart Failure | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Postoperative Vasoplegia | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Respiratory Failure Requiring Reintubation | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Acute Kidney Injury | Using the Akin definition | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation | Posted | Count of Participants | Participants | 30 days |
|
|
|
| Secondary | Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation | Posted | Count of Participants | Participants | 30 days |
|
|
|
| 1 |
| 76 |
| 1 |
| 76 |
| 29 |
| 76 |
| EG001 | Group B | Beta Blockers and Ascorbic Acid beta blockers: metoprolol 25mg by mouth every 6 hours ascorbic acid: 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 | 1 | 74 | 3 | 74 | 29 | 74 |
| EG002 | Group C | Beta Blockers and Amiodarone beta blockers: metoprolol 25mg by mouth every 6 hours amiodarone: 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 | 1 | 78 | 1 | 78 | 21 | 78 |
| EG003 | Group D | Beta Blockers alone beta blockers: metoprolol 25mg by mouth every 6 hours | 0 | 76 | 1 | 76 | 27 | 76 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D001572 | Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D006880 | Hydroxy Acids |
| D002241 | Carbohydrates |