Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery (MINA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Abdallah Alameddine, Baystate Medical Center
ClinicalTrials.gov Identifier:
NCT01422148
First received: August 17, 2011
Last updated: June 4, 2014
Last verified: June 2014

August 17, 2011
June 4, 2014
October 2011
October 2014   (final data collection date for primary outcome measure)
Atrial fibrillation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01422148 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery
Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery (MINA)

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Atrial Fibrillation
  • Drug: Amiodarone
    oral amiodarone (400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days
    Other Name: amiodarone
  • Drug: Minocycline
    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
    Other Name: Minocin
  • Amiodarone
    oral amiodarone
    Intervention: Drug: Amiodarone
  • Experimental: minocycline
    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
    Interventions:
    • Drug: Amiodarone
    • Drug: Minocycline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
400
December 2014
October 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

-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.

Exclusion Criteria:

  • 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),
  • thyrotoxicosis,
  • pregnancy,
  • 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).

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01422148
BH-09-176
Yes
Abdallah Alameddine, Baystate Medical Center
Baystate Medical Center
Not Provided
Principal Investigator: Abdallah k Alameddine, MD Baystate Medical Center
Baystate Medical Center
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP