Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

• ClinicalTrials.gov Identifier: NCT00953212
• Recruitment Status: Completed
• First Posted: August 6, 2009
• Results First Posted: March 29, 2018
• Last Update Posted: April 26, 2018
• Sponsor: MaineHealth
• Information provided by (Responsible Party): Peter C. Donovan, MaineHealth

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Atrial Flutter	Drug: beta blockers; Drug: amiodarone; Drug: ascorbic acid	Phase 3

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 304 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Study Start Date: August 2009
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: February 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group A; Beta Blockers, Ascorbic Acid and Amiodarone	Drug: beta blockers; metoprolol 25mg by mouth every 6 hours; Other Names: Lopressor; Toprol XL; Drug: 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; Other Name: Cordarone; Drug: 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; Other Name: vitamin C
Active Comparator: Group B; Beta Blockers and Ascorbic Acid	Drug: beta blockers; metoprolol 25mg by mouth every 6 hours; Other Names: Lopressor; Toprol XL; Drug: 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; Other Name: vitamin C
Active Comparator: Group C; Beta Blockers and Amiodarone	Drug: beta blockers; metoprolol 25mg by mouth every 6 hours; Other Names: Lopressor; Toprol XL; Drug: 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; Other Name: Cordarone
Active Comparator: Group D; Beta Blockers alone	Drug: beta blockers; metoprolol 25mg by mouth every 6 hours; Other Names: Lopressor; Toprol XL

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. Number of Participants With Mortality [ Time Frame: 30 days ]
   Mortality measured within length of hospital stay
2. Hospital Length of Stay [ Time Frame: 30 days ]
3. ICU Length of Stay [ Time Frame: 30 days ]
4. Number of Participants With Stroke [ Time Frame: 30 days ]
   Cerebral vascular accident occurring within hospital length of stay
5. Number of Participants With Low Output Heart Failure [ Time Frame: 30 days ]
6. Number of Participants With Postoperative Vasoplegia [ Time Frame: 30 days ]
7. Number of Participants With Respiratory Failure Requiring Reintubation [ Time Frame: 30 days ]
8. Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement [ Time Frame: 30 days ]
9. Number of Participants With Acute Kidney Injury [ Time Frame: 30 days ]
   Using the Akin definition
10. Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation [ Time Frame: 30 days ]
11. Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation [ Time Frame: 30 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Maine

Maine Medical Center

Portland, Maine, United States, 04102

Sponsors and Collaborators

MaineHealth

Investigators

• Principal Investigator: Peter C Donovan, PA-C, MHS; MaineHealth
• Study Chair: Robert S Kramer, M.D.; MaineHealth

More Information

• Responsible Party: Peter C. Donovan, Staff Physician Assistant, Cardiothoracic Surgery, MaineHealth
• ClinicalTrials.gov Identifier: NCT00953212
• Other Study ID Numbers: MMC-3514
• First Posted: August 6, 2009
• Results First Posted: March 29, 2018
• Last Update Posted: April 26, 2018
• Last Verified: March 2018

Keywords provided by Peter C. Donovan, MaineHealth:

atrial fibrillation; cardiac surgery; open heart surgery

Additional relevant MeSH terms:

Atrial Fibrillation; Atrial Flutter; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Ascorbic Acid; Amiodarone; Metoprolol; Adrenergic beta-Antagonists; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Anti-Arrhythmia Agents; Vasodilator Agents; Potassium Channel Blockers; Membrane Transport Modulators; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents