Short Term Anti-aRrhythmic Therapy for Post-Operative AF in Cardiac Surgery Patients Pilot Trial (START-POAF)

Short Term Anti-aRrhythmic Therapy for Post-Operative AF in Cardiac Surgery Patients (START-POAF) Pilot Trial

The START-POAF pilot study is a prospective, open-label two-arm, randomized controlled trial with blinded assessment of outcomes (PROBE). This pilot study will assess Atrial Fibrillation (AF) recurrence and burden in patients with new-onset AF following cardiac surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation New Onset
• Intervention / Treatment: Drug: Amiodarone Hydrochloride 200 MG

Detailed Description

Atrial fibrillation (AF) is the most common abnormal heart rhythm in the world. In patients who have cardiac surgery, new AF is found as an early complication in more than one out of every four surgeries. In the weeks and months after heart surgery, patients who have new AF take a medication called amiodarone to keep their heart in rhythm as it heals. If the heart goes back into AF, patients can have symptoms of heart racing, heart failure (fluid on the lungs) or stroke. Although amiodarone is effective, it can have side effects like dizziness, nausea and slow heart rate. It may also damage the lungs, liver and thyroid gland. Many patients are not able to complete their full prescribed course after surgery. Therefore, it is crucial that the investigators find the shortest possible length of treatment with amiodarone that will keep the heart in rhythm while minimizing the chance of side effects or organ damage. The START-POAF Pilot Randomized Trial will compare two different durations of amiodarone treatment: 1) in-hospital load only and 2) in-hospital load plus 4 weeks after loading dose. All participants will wear an electrocardiogram (ECG) monitor for 4 weeks the day after they complete their loading dose. The investigators will compare the amount of AF seen on the ECG between the two groups.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ingrid Copland; Phone Number: 905-512-4940; Email: start-poaf@phri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years;
2. Have undergone cardiac surgery including CABG, valve surgery, ascending aorta replacement, or combinations thereof within 14 days of randomization;
3. Had new-onset POAF (or flutter), documented by 12-lead ECG or lasting ≥ 1 hour on telemetry. Patients can be in AF or sinus rhythm at the time of randomization;
4. Expected to receive 3 g - 5 g of amiodarone loading dose post-surgery.
5. Expected to be ready for hospital discharge within 48 h of randomization.

Exclusion Criteria:

1. Documented preoperative history of paroxysmal, persistent or permanent AF;
2. Planned use of a class I or III anti-arrhythmic drug (other than study drug);
3. Patients who have undergone heart transplant, complex congenital heart surgery, isolated ventricular assist device insertion, or AF ablation (surgical or catheter);
4. Known allergy to ECG adhesives;
5. Contraindication to amiodarone (i.e. hyperthyroidism, severe restrictive or obstructive lung disease, Long QT syndrome, PR > 240 ms, high-grade AV block).
6. Individuals who are pregnant, breastfeeding, or of childbearing potential - female subjects, premenopausal who are not surgically sterile, or, if sexually active not practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, who have a positive pregnancy test at screening

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: Amiodarone maintenance therapy; Amiodarone 200 mg daily for four weeks	Drug: Amiodarone Hydrochloride 200 MG; 200 mg daily for 4 weeks; Other Names: Cordarone; Pacerone
No Intervention: No Amiodarone maintenance therapy; No ongoing Amiodarone maintenance therapy for four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 patients per center per month	Ability to recruit an average of 3 participants per center per month	2 years
Less than 10% cross-over rate	Less than 10% cross-over rate	28 days
Intervention group taking at least 80% of their amiodarone 4 week maintenance therapy	Greater than and equal to 90% of the intervention group taking at least 80% of their amiodarone 4 week maintenance therapy	28 days
90% follow-up at 30 days	Greater than and equal to 90% follow-up at 30 days	At 30 days post randomization date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burden of atrial fibrillation	Defined as percent time in atrial fibrillation	In the 28 days measured by the continuous ECG monitor placed on the day after the participant finishes their 3-5g amiodarone loading dose
Time to first AF > 6 minutes, >6 hours and >24 hours	Time to first AF > 6 minutes, >6 hours and >24 hours reported from the continuous ECG monitor	In the 28 days measured by the continuous ECG monitor placed on the day after the participant finishes their 3-5g amiodarone loading dose
Participants with at least one episode >6 minutes, >6 hours and >24 hours	Proportion of participants with at least one episode > 6 minutes, >6 hours and >24 hours reported from the continuous ECG	In the 28 days measured by the continuous ECG monitor placed on the day after the participant finishes their 3-5g amiodarone loading dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Failure	Number of participants who experience heart failure	90 days after randomization
Atrial Fibrillation	Number of participants who experience atrial fibrillation	90 days after randomization
A composite of stroke, myocardial infarction and cardiovascular death	Number of participants who have at least one of the following: stroke, myocardial infarction or cardiovascular death	90 days after randomization
Major bleeding	Number of participants who experience a major bleed	90 days after randomization
Systemic arterial embolism	Number of participants who experience a systemic arterial embolism	90 days after randomization
Atrial Fibrillation Effect on QualiTy of life (AFEQT) Questionnaire	The Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT) evaluates symptoms, daily activities, and treatment concerns participants have related to atrial fibrillation and will be completed on all participants	Collected at baseline, 30 day follow-up and 90 day follow-up
SF-12 Questionnaire	The SF-12 questionnaire which assesses physical and mental health will be completed on all participants	Collected at baseline, 30 day follow-up and 90 day follow-up
Electrical cardioversion	Proportion of participants who undergo electrical cardioversion	Randomization to 90 days

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: William McIntyre, MD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 23, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; amiodarone; heart rhythm monitoring
• 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: 2023.START-POAF

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