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

NCT ID: NCT01422148

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2028-01-24

Brief Summary

. New- onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and its occurrence increases with age. POAF can result in clinically significant morbidity and mortality. The national trend in the US is that the population older than 65 years is increasing, making healthcare expenditure related to POAF to be a major burden on health care system. Effective treatment of POAF is imperative in ensuring quality of care and reduction of costs.

In 2021 there is a projected total of 377,763 cardiovascular surgeries in the US alone with approximately half of which will have POAF with longer postoperative length of stay (+3.9 days) and higher discharge costs (+$13,993) than no-POAF patients (Reference: Ann Thorac Surg. 2015 Jan;99(1):109-14). Amiodarone, the currently used therapy, is often insufficient to prevent POAF and has multiple side-effects. In this study, we expect to improve the incidence of POAF by using a common acne drug (Minocycline) that is safe and that could be incorporated in clinical care of this disease.

Detailed Description

New-onset postoperative atrial fibrillation after cardiac surgery (POAF) is commonly observed and it increases morbidity, mortality, and health care expenditure. Amiodarone administration is proposed initial agent for prevention and treatment of POAF, but while useful, this drug has a number of adverse side-effects and relapse requiring anticoagulation therapy at hospital discharge is prevalent. Effective medications are needed with respect to management. Minocycline, an old tetracycline antibiotic, has additional effects including inhibition of atrial myocyte apoptosis.The finding that apoptosis of right atrial myocytes is thought to be one etiologic factor underlying POAF supports examining the hypothesis in this project that adding minocycline to amiodarone could favorably reduce POAF frequency rate. Minocycline has been used for over four decades and has a good safety profile, therefore this investigation is not a phase I trial. With a limited sample size, while the data of our MINAA Exploratory trial (the Minocycline Plus Amiodarone Versus Amiodarone Alone for the Prevention of Atrial Fibrillation After Cardiac Surgery) were not sufficient to draw definite conclusions, rather they suggested feasibility of such therapy in this cohort. In the current pilot study, we assess the clinical effectiveness and safety of minocycline plus amiodarone in preventing POAF with a larger cohort of two parallel groups (n=40, each) randomly assigned in a 1:1 ratio.In this trial we compare 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, for prevention of POAF among adult patients undergoing coronary artery bypass grafts, heart valve repair or replacement, 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.The primary outcome is a newly detected POAF by telemetry, Holter monitoring, or by daily wireless ECG sensors within 6 weeks from the time of randomization. Composite secondary outcomes include death at 30 days, length of hospital stay, and other adverse events.To elucidate how minocycline causally elicits its pharmacologic effects, sera sampling of biomarkers such as NF-Kappa B, cleaved caspase-3, and NT-pro-BNP are measured pre-procedure, then on the 3rd and 5th postoperative days. If the proposed intervention is successful, it underscores what can ensue when the target evolves to the common population level requiring a nuanced approach pursued by Phase III-IV proposals

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Amiodarone

oral amiodarone

Group Type: OTHER

Amiodarone

Intervention Type: DRUG

oral amiodarone (400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days

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

Group Type: EXPERIMENTAL

Amiodarone

Intervention Type: DRUG

oral amiodarone (400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days

Minocycline

Intervention Type: DRUG

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

Amiodarone

oral amiodarone (400 mg twice daily for 7 days, then 200 mg twice daily for the next 7 days

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Minocin

Eligibility Criteria

Inclusion Criteria

Inclusion criteria are adults, including women and minorities > 18 years of age, who are also willing to participate for the duration of the trial (6 weeks). All non-congenital cardiac operations are included: Coronary Artery Bypass Graft, valve repair/replacement, or combination of CABG and heart valve operations. Patients should be able to access iPhones and download ECGs using their electronic Devices.

Exclusion Criteria

Exclusion criteria Patients with prior (within 6 months) or current atrial fibrillation (AF) or flutter, patients undergoing concomitant surgical AF ablation or a history of AF, transcatheter aortic valve replacement or other minimally invasive procedures, 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) are excluded. Other exclusion criteria are the following: thyrotoxicosis, pregnancy, severe chronic obstructive pulmonary disease (COPD, with FEV1/FVC <70%), recent history of drug or alcohol abuse, and intolerance to tetracycline or amiodarone. Because a core scientific basis of this trial concerning the role of underlying atrial tissue inflammatory/apoptotic 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 (>10 days) oral corticosteroids (prednisolone > 10mg or other), or estrogen replacement; and finally patients with newly diagnosed cancer (<5 years) are also excluded.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baystate Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Abdallah Alameddine

Medical Staff

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abdallah k Alameddine, MD

Role: PRINCIPAL_INVESTIGATOR

Baystate Medical Center

Locations

Abdallah Alameddine

Melrose, Massachusetts, United States

Countries

United States

Central Contacts

Abdallah Alameddine, MD

Role: CONTACT

akalameddine@gmail.com

17815212074

Abdallah k Alameddine, md

Role: CONTACT

akalameddine@gmail.com

413 794-0000 ext. 5303

Facility Contacts

Abdallah Alameddine, MD

Role: primary

akalameddine@gmail.com

781-521-2074

Other Identifiers

BH-09-176

Identifier Type: -

Identifier Source: org_study_id