Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

Phase 3

Completed

Conditions: Atrial Fibrillation
Atrial Flutter

Interventions: Drug: beta blockers
Drug: amiodarone
Drug: ascorbic acid

Registration Number: NCT00953212

Lead Sponsor: MaineHealth

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 304

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group C	beta blockers	Beta Blockers and Amiodarone
Group A	beta blockers	Beta Blockers, Ascorbic Acid and Amiodarone
Group B	beta blockers	Beta Blockers and Ascorbic Acid
Group D	beta blockers	Beta Blockers alone
Group A	amiodarone	Beta Blockers, Ascorbic Acid and Amiodarone
Group A	ascorbic acid	Beta Blockers, Ascorbic Acid and Amiodarone
Group B	ascorbic acid	Beta Blockers and Ascorbic Acid
Group C	amiodarone	Beta Blockers and Amiodarone

Primary Outcome Measures

Name	Time	Method
Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery	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

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