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Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery

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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:
Information provided by (Responsible Party):
Peter C. Donovan, Maine Medical Center

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 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


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




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 ]


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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

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

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
Results First Posted: March 29, 2018
Last Update Posted: April 26, 2018
Last Verified: March 2018

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