Amiodarone and N-Acetylcysteine or Amiodarone Alone for Preventing Atrial Fibrillation After Thoracic Surgery

A Randomized, Double-Blind, Controlled Trial of Combined Amiodarone and N-Acetylcysteine Versus Amiodarone Plus Placebo for the Prevention of Atrial Fibrillation in High Risk Patients Undergoing Thoracic Surgery

This trial will be comparing the combination of amiodarone and NAC (n=122) to amiodarone alone and NAC matched placebo (n=122) to determine the rates with which sustained (lasting >30 seconds) or clinically significant POAF is reduced in high risk patients within 7 days after major thoracic surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Thoracic Surgery; Atrial Fibrillation in High Risk Patients
• Intervention / Treatment: Drug: Placebo; Drug: Amiodarone; Drug: N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • University of Washington School of Medicine in St. Louis
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memorial Sloan Kettering Basking Ridge (Consent only)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Consent only)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Consent only)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack (Consent only)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Consent only)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville Centre (Consent only)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Consent only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥18 years old scheduled for elective thoracic surgery (segmentectomy, lobectomy or bi-lobectomy, pneumonectomy or esophagectomy) and meeting one of the four following risk criteria:

  • 1. Female & BNP ≥ 25pg/ml (no age limit)
  • 2. Male gender <75 & BNP ≥ 25pg/ml
  • 3. Male- age ≥75 (No BNP limit)
  • 4. History of prior AF
• Patients in sinus rhythm.
• Patients with stable respiratory status (no respiratory distress).
• Patients capable of providing written, informed consent.

Exclusion Criteria:

• Patients scheduled for extrapleural pneumonectomy.
• Hemodynamically unstable patients (not in cardiogenic shock or having an acute MI).
• Patients with 2nd or 3rd degree atrioventricular (AV) block.
• Patients with hypersensitivity to amiodarone or NAC.
• Patients already taking class Ic or III antiarrhythmic drugs.
• Hepatic insufficiency (≤2 times the upper normal limit of transaminase levels).
• Renal insufficiency (creatinine ≥2.0 mg/dl).
• Known pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Amiodarone + Placebo; Amiodarone loading: 150 mg IV in PACU over one hour, then 1.0 gm/24h x 2 + NAC loading matching placebo; 50 mg/kg IV in PACU over one hour, then 50 mg/kg/24h x 2 NAC matched placebo continuously for 48 hours.	Drug: Placebo; Drug: Amiodarone
Experimental: Amiodarone + N-Acetylcysteine; Amiodarone loading: 150 mg IV in PACU over one hour, then 1.0 gm/24h x 2 + NAC loading: 50 mg/kg IV in PACU over one hour, then 50 mg/kg/24h x 2 and then continuously for 48 hours.	Drug: Amiodarone; Drug: N-Acetylcysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of sustained (lasting >30 seconds) or clinically significant post-operative atrial fibrillation (POAF)	Atrial arrhythmias will be considered and defined as atrial fibrillation/flutter (AF) lasting great than 30 seconds and/or sustained supraventricular tachycardia (SVT) that are detected by continuous telemetry or that are clinically significant, requiring intervention and documented by 12-lead ECG by the clinical staff.	within 7 days since operation

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Washington University School of Medicine; The Cleveland Clinic; Vanderbilt University School of Medicine
• Investigators: Principal Investigator: David Amar, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Anticipated): April 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: April 21, 2016
• First Submitted That Met QC Criteria: April 22, 2016
• First Posted (Estimate): April 25, 2016

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: N-Acetylcysteine; Amiodarone; 16-307
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protective Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Expectorants; Potassium Channel Blockers; Acetylcysteine; N-monoacetylcystine; Amiodarone
• Other Study ID Numbers: 16-307