Repeated Amiodarone Dosing In Cardiac surgicaL Procedures (RADICAL)

This study is a single-center, prospective, randomized, open-label trial of subjects who develop atrial fibrillation after non-emergent cardiac surgery at the University of Kentucky Chandler Medical Center (UKCMC). Patients will be randomized to receive either a conventional amiodarone dosing regimen (CDR) or a repeated amiodarone bolus dosing regimen (RBDR).

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: AMIODARONE

Detailed Description

This study will screen and consent approximately 150 patients undergoing non-emergent cardiac surgery. Approximately 60 of these patients are likely to develop stable postoperative atrial fibrillation (POAF) in the postoperative period. Amiodarone is commonly given as an initial intravenous (IV) bolus (150 mg IV) followed by a combined IV and oral load to a total dose of 8 gm. Because of amiodarone's beta-blocker activity, the IV bolus in patients with POAF is associated with a reduced heart rate that may lead to restoration of NSR. For this reason, some clinicians will provide up to 5 additional IV amiodarone boluses during the drug's loading period to treat RVR.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject must be 18 years old or older
• Subject must be willing to give written informed consent
• Subject must undergo or scheduled for non-emergent cardiac surgery, including coronary artery bypass grafting (CABG), non-infectious valve repair or replacement, atrial or septal defect repair, thoracic aortic replacement surgery, or any combination of these procedures

Exclusion Criteria:

• Documented allergy to amiodarone or iodine
• History of atrial fibrillation or other heart conduction system abnormality
• History of cardiac maze, pulmonary vein isolation, or other procedure affecting the conduction system
• Scheduled cardiac maze, pulmonary vein isolation, or other procedure affecting the conduction system
• Low cardiac index or cardiogenic shock requiring pharmacologic or mechanical support
• History of pre-existing respiratory system disease requiring oxygen therapy prior to admission
• History of cirrhosis or other chronic liver diseases
• Pregnancy or breastfeeding mothers
• Prisoner status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional amiodarone dosing regimen (CDR); Initial amiodarone bolus of 150 mg IV over 10 minutes then a 24-hour amiodarone loading infusion (1 mg/min for 6 hours followed by 0.5 mg/min for 18 hours), followed by enteral (400 mg amiodarone oral or per tube three times daily or 2 times daily if the patient has gastrointestinal intolerance when taking the drug three times daily) or intravenous amiodarone (0.5 mg/min continuous infusion) to complete an 8-gm total amiodarone load. Maintenance amiodarone (200 mg amiodarone oral or per tube once daily) at discretion of attending physician.	Drug: AMIODARONE; Assess the effectiveness of different dosing strategies of amiodarone.
Active Comparator: Repeated amiodarone bolus dosing regimen (RBDR); Initial amiodarone bolus of 150 mg IV over 10 minutes, then 1.0 mg/min IV amiodarone infusion for 6 hours, then a 0.5 mg/min IV amiodarone infusion for 18 hours, followed by enteral (400 mg amiodarone oral or per tube three times daily or 2 times daily if the patient has gastrointestinal intolerance when taking the drug three times daily) or intravenous amiodarone (0.5 mg/min continuous infusion) to complete an 8-gm total amiodarone load. In addition, patients in the RBDR will receive an additional 150 mg IV amiodarone bolus whenever the patient develops tachycardia (Heart Rate (HR) = 110 beats per minute) lasting more than 10 minutes. This bolus may be repeated up to a total of 5 times (6 total boluses) over the first 24 hours. Maintenance amiodarone (200 mg amiodarone oral or per tube once daily) at discretion of attending physician.	Drug: AMIODARONE; Assess the effectiveness of different dosing strategies of amiodarone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal Sinus Rhythm -24 HRS	Percentage of patients who develop stable POAF after non-emergent cardiac surgery, the percentage of patients who have converted to NSR at 24-hours after receiving a repeated amiodarone bolus and loading dose regimen to the percentage of patients who have converted to NSR after a conventional amiodarone IV loading dose regimen.	24-hours after receiving amiodarone bolus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Target Heart Rate Time	Total time, in minutes, during the first 24 hours that the patient achieves target HR (HR < 110 bpm) between patients who receive a repeated amiodarone bolus dosing regimen and those who receive a conventional amiodarone bolus dosing regimen	24-hours after receiving amiodarone bolus
Time to Target Heart Rate	Time to achieve target HR (HR < 110 bpm) between patients who receive a repeated amiodarone bolus dosing regimen and those who receive a conventional amiodarone bolus dosing regimen	24-hours after receiving amiodarone bolus
Normal Sinus Rhythm -Hospital Index	Percentage of patients who achieve NSR by ICU discharge and hospital discharge between patients who receive a repeated amiodarone bolus dosing regimen and those who receive a conventional amiodarone bolus dosing regimen	duration of ICU and hospital visit, up to 20 days
Recurrent AF	Percentage of patients who have recurrent AF before ICU discharge and before hospital discharge and patients who receive a repeated amiodarone bolus dosing regimen and those who receive a conventional amiodarone bolus dosing regimen	duration of ICU and hospital visit, up to 20 days

Collaborators and Investigators

• Sponsor: Kevin W Hatton, MD, PhD
• Investigators: Principal Investigator: Kevin Hatton, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): October 10, 2022
• Study Completion (Actual): October 10, 2022

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Enzyme Inhibitors; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Sodium Channel Blockers; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Potassium Channel Blockers; Amiodarone
• Other Study ID Numbers: 67919

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No