Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00953212
• Other study ID #: MMC-3514
• Status: Completed
• Phase: Phase 3
• First received: August 5, 2009
• Last updated: March 28, 2018
• Start date: August 2009
• Est. completion date: February 2012

Study information

• Verified date: March 2018
• Source: Maine Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: February 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Flutter

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	Maine Medical Center	Portland	Maine

Sponsors (1)

Lead Sponsor	Collaborator
Maine Medical Center

Country where clinical trial is conducted

United States, 

Outcome

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