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
  Purpose

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.


Condition Intervention
Atrial Fibrillation
Drug: Amiodarone
Drug: Minocycline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery (MINA)

Resource links provided by NLM:


Further study details as provided by Baystate Medical Center:

Primary Outcome Measures:
  • Atrial fibrillation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: October 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Amiodarone
oral amiodarone
Drug: Amiodarone
oral amiodarone (400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days
Other Name: 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
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01422148

Locations
United States, Massachusetts
Baystate Medical Center
Springfield, Massachusetts, United States, 01107
Sponsors and Collaborators
Baystate Medical Center
Investigators
Principal Investigator: Abdallah k Alameddine, MD Baystate Medical Center
  More Information

No publications provided

Responsible Party: Abdallah Alameddine, Medical Staff, Baystate Medical Center
ClinicalTrials.gov Identifier: NCT01422148     History of Changes
Other Study ID Numbers: BH-09-176
Study First Received: August 17, 2011
Last Updated: June 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Baystate Medical Center:
cardiac surgery
atrial fibrillation
minocycline
amiodarone

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Minocycline
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 27, 2014