We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00953212
Recruitment Status : Completed
First Posted : August 6, 2009
Last Update Posted : May 11, 2012
Sponsor:
Information provided by (Responsible Party):

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
Primary Completion Date : January 2012
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. Occurence of post-operative atrial fibrillation requiring treatment after open heart surgery [ Time Frame: 5 postoperative days ]

Secondary Outcome Measures :
  1. Mortality [ Time Frame: 30 days ]
  2. Hospital Length of Stay [ Time Frame: 30 days ]
  3. ICU Length of Stay [ Time Frame: 30 days ]
  4. Stroke [ Time Frame: 30 days ]
  5. Low Output Heart Failure [ Time Frame: 30 days ]
  6. Postoperative Vasoplegia [ Time Frame: 30 days ]
  7. Respiratory Failure requiring reintubation [ Time Frame: 30 days ]
  8. Bradycardia necessitating permanent pacemaker placement [ Time Frame: 30 days ]
  9. Acute Kidney Injury [ Time Frame: 30 days ]
  10. Readmission to ICU for treatment of atrial fibrillation [ Time Frame: 30 days ]
  11. Readmission to hospital for treatment of atrial fibrillation [ Time Frame: 30 days ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00953212


Locations
United States, Maine
Maine Medical Center
Portland, Maine, United States, 04102
Sponsors and Collaborators
Maine Medical Center
Investigators
Principal Investigator: Peter C Donovan, PA-C, MHS Maine Medical Center
Study Chair: Robert S Kramer, M.D. Maine Medical Center
More Information

Responsible Party: Peter C. Donovan, Staff Physician Assistant, Cardiothoracic Surgery, Maine Medical Center
ClinicalTrials.gov Identifier: NCT00953212     History of Changes
Other Study ID Numbers: MMC-3514
First Posted: August 6, 2009    Key Record Dates
Last Update Posted: May 11, 2012
Last Verified: May 2012

Keywords provided by Peter C. Donovan, Maine Medical Center:
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
Adrenergic beta-Antagonists
Amiodarone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter 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