Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery
Information source: Baystate Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Atrial Fibrillation
Intervention: Amiodarone (Drug); Minocycline (Drug)
Status: Active, not recruiting
Sponsored by: Baystate Medical Center
Official(s) and/or principal investigator(s):
Abdallah k Alameddine, MD, Principal Investigator, Affiliation: Baystate Medical Center
Postoperative atrial fibrillation (POAF) is a common complication after heart surgery.
Amiodarone is the drug of choice to treat POAF. Inflammation is considered one of underlying
factor for POAF. Minocycline is an antibiotic with anti-inflammatory properties.
Official title: Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery (MINA)
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention
Primary outcome: Atrial fibrillation
Currently, the most effective therapy to prevent PAF after cardiac surgery remains
undetermined. Amiodarone administration should be considered to decrease the incidence of
new-onset postoperative atrial fibrillation (PAF) after cardiac operations. However, PAF
requiring anticoagulation therapy occurs in 40-50% of cases early after cardiac surgery
despite amiodarone prophylaxis. PAF is associated with increased morbidity and mortality
including complications resulting from long-term anticoagulation. The findings that an
exaggerated inflammatory response manifested by elevated acute oxidative stress proteins,
and the induction of apoptotic mediators in right atrial myocytes may be responsible for
PAF, and that steroidal or non-steroidal anti-inflammatory drug therapy can reduce PAF
support this mechanism as a possible etiological factor. Minocycline, a tetracycline
antibiotic, has specific atrial myocyte anti-apoptotic effect which decreases right atrial
tissue inflammation, oxidative stress activity and molecular indices of apoptosis.
Apoptosis of cardiac myocytes is thought to be one etiologic factor underlying postoperative
atrial fibrillation. These observations lead to this trial hypothesis that the addition of
minocycline to amiodarone may favorably affect suppression of PAF. This randomized
controlled trial compares the efficacy and safety of treatment effects of intravenous
minocycline 100 mg daily x 5 days starting intra-operatively combined with oral amiodarone
(400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days), versus the
same dose oral amiodarone alone, in the prevention of PAF among adult patients undergoing
coronary artery bypass grafts, heart valve replacement/repair, or combined procedures. All
patients receive 150 mg intravenous amiodarone intraoperatively and a 2nd similar dose of
amiodarone bolus is permitted for tachyarrhythmia any time within 24 hours after surgery.
PAF is detected by telemetry during hospitalization and 2 weeks following hospital
discharge, by a 12-lead electrocardiogram. The primary outcome is PAF occurrence.
Secondary outcomes include thromboembolic stroke, need for pharmacologic or electric
cardioversion, mediastinal exploration for anticoagulation-related bleeding, serious drug
side effects, Clostridium difficile superinfection, length of hospital stay and 30-day
mortality from cardiovascular causes. Based on a projected PAF incidence of 26% and
assuming 5% dropout rate and a two-sided alpha of 0. 05, this design requires 400 subjects to
detect a reduction of 50% in the primary outcome with 90% power. This is a valuable trial
that would affect the method in which the investigators practice.
Minimum age: 18 Years.
Maximum age: N/A.
- Eligibility criteria includes all non-congenital cardiac operations are included:
- coronary artery bypass graft (CABG),
- valve repair/replacement, or
- combination of CABG and heart valve operations.
- prior (within 6 months) or current PAF or flutter,
- prior cerebrovascular event,
- cardiogenic shock or resuscitation,
- evidence of hepatic or renal dysfunctions (i. e., an alanine aminotransferase level
that is ≥ twice the upper limit of the normal range, or either a serum creatinine
level that is ≥ 2. 0 mg/dL or need for preoperative dialysis),
- severe COPD (FEV1/FVC <70%),
- recent history of drug or alcohol abuse, and
- intolerance to tetracycline or amiodarone.
Finally, because a core scientific basis of the trial concerned the role of underlying
atrial tissue inflammatory activity, patients with inflammatory conditions such as lupus,
severe arthritis, thyroiditis or inflammatory bowel disease are excluded; as are patients
taking preoperative immunosuppressant agents, long-term oral corticosteroids, or estrogen
replacement; and a newly diagnosed cancer (<5 years).
Locations and Contacts
Baystate Medical Center, Springfield, Massachusetts 01107, United States
Starting date: October 2011
Last updated: July 20, 2015