Clinical trial NCT00953212: Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Atrial Flutter
Keywords: atrial fibrillation
cardiac surgery
open heart surgery
Lead sponsor: MaineHealth
Sponsor class: OTHER
First posted: 2009-08-06
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery
timeFrame: 5 postoperative days
Secondary outcomes:
measure: Number of Participants With Mortality
timeFrame: 30 days
measure: Hospital Length of Stay
timeFrame: 30 days
measure: ICU Length of Stay
timeFrame: 30 days
measure: Number of Participants With Stroke
timeFrame: 30 days
measure: Number of Participants With Low Output Heart Failure
timeFrame: 30 days
measure: Number of Participants With Postoperative Vasoplegia
timeFrame: 30 days
measure: Number of Participants With Respiratory Failure Requiring Reintubation
timeFrame: 30 days
measure: Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement
timeFrame: 30 days
measure: Number of Participants With Acute Kidney Injury
timeFrame: 30 days
measure: Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation
timeFrame: 30 days
measure: Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation
timeFrame: 30 days
Other outcomes:
Locations:
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
Study officials:
affiliation: MaineHealth
name: Peter C Donovan, PA-C, MHS
role: PRINCIPAL_INVESTIGATOR
affiliation: MaineHealth
name: Robert S Kramer, M.D.
role: STUDY_CHAIR
References: