Prophylaxis for Patients at Risk to Eliminate Post-operative Atrial Fibrillation

NCT ID: NCT04392921

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-07
• Study Completion Date: 2024-04-30

Brief Summary

After surgery on the lungs or esophagus, 12-46% of patients experience an irregular heart rhythm called atrial fibrillation. Although usually transient, post-operative atrial fibrillation is associated with longer stay in hospital, greater complications, and increased risk of death. Several medications have been shown to be effective at reducing the risk of atrial fibrillation after their surgery with the greatest effectiveness and safety demonstrated with amiodarone. Nevertheless, amiodarone has potential side effects, and so it is only recommended in patients with increased risk of developing atrial fibrillation. A tool has been developed and validated to identify high-risk patients but no clinical trial has looked at the effectiveness of administering amiodarone in this high-risk group. This study aims to assess the feasibility and safety of conducting a clinical trial where patients are randomized to receive amiodarone or placebo. This is critical before considering a full-scale trial to assess the effectiveness of amiodarone in reducing atrial fibrillation after surgery on the lungs or esophagus.

Conditions

Atrial Fibrillation

Study Design

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

Study Groups

Intervention Arm

Patients randomized to amiodarone treatment

Group Type: EXPERIMENTAL

Amiodarone

Intervention Type: DRUG

Patients will undergo one of the two regimens of amiodarone, based on their ability to tolerate po (per os) intake in the post-operative period:

• All patient will receive 1050mg of amiodarone in 100mL of 5% dextrose administered intravenously initiated at the time of anesthesia induction at a rate of 0.73mg/min or 43.75mg/h and continued over 24 hours followed by:

• If able to tolerate po intake: 400mg po BID for post-operative days 1 to 5 or until the day of discharge (whichever occurs first).
• If unable to tolerate po intake: daily infusion of 1050mg in 100mL of 5% dextrose for postoperative days 1 to 5 or until the day of discharge (whichever occurs first).

Control Arm

Patients randomized to placebo treatment

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will undergo one of the two schedules or intravenous infusion, based on their ability to tolerate po intake in the post-operative period:

• All patients will receive 100mL of 5% dextrose administered intravenously initiated at the time of anesthesia induction at a rate of 0.73mg/min or 43.75mg/h and continued over 24 hours followed by:

o If able to tolerate po intake: 400mg po BID for post-operative days 1 to 5 or until the day of discharge (whichever occurs first).

• Esophagectomy patient will receive 100mL of 5% dextrose at the time of anesthesia induction at a rate of what would be 0.73mg/min or 43.75mg/h if it contained 1050mg of amiodarone, followed by daily infusion of 100mL of 5% dextrose for 4 days or until the day of discharge (whichever occurs first).

Interventions

Amiodarone

Patients will undergo one of the two regimens of amiodarone, based on their ability to tolerate po (per os) intake in the post-operative period:

• All patient will receive 1050mg of amiodarone in 100mL of 5% dextrose administered intravenously initiated at the time of anesthesia induction at a rate of 0.73mg/min or 43.75mg/h and continued over 24 hours followed by:

• If able to tolerate po intake: 400mg po BID for post-operative days 1 to 5 or until the day of discharge (whichever occurs first).
• If unable to tolerate po intake: daily infusion of 1050mg in 100mL of 5% dextrose for postoperative days 1 to 5 or until the day of discharge (whichever occurs first).

Intervention Type: DRUG

Placebo

Patients will undergo one of the two schedules or intravenous infusion, based on their ability to tolerate po intake in the post-operative period:

• All patients will receive 100mL of 5% dextrose administered intravenously initiated at the time of anesthesia induction at a rate of 0.73mg/min or 43.75mg/h and continued over 24 hours followed by:

o If able to tolerate po intake: 400mg po BID for post-operative days 1 to 5 or until the day of discharge (whichever occurs first).

• Esophagectomy patient will receive 100mL of 5% dextrose at the time of anesthesia induction at a rate of what would be 0.73mg/min or 43.75mg/h if it contained 1050mg of amiodarone, followed by daily infusion of 100mL of 5% dextrose for 4 days or until the day of discharge (whichever occurs first).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged 18 years or greater
• Undergoing major non-cardiac pulmonary or esophageal surgery (including esophagectomy, pulmonary wedge resection, lobar resection, pneumonectomy, or gastrectomy)
• POAF prediction score greater than or equal to 4

Exclusion Criteria

• Aged less than 18 years
• History of atrial arrhythmia (paroxysmal or persistent), or Wolf-Parkinson-White syndrome (WPW), or 2nd or 3rd degree heart block without a pacemaker
• Current antiarrythmic therapy (including amiodarone, propafenone, sotalol, flecainide, and dronedarone)
• Previous severe adverse reaction or contraindication to amiodarone (including pre-existing interstitial lung disease, or history of hepatotoxicity from amiodarone)
• QTc interval longer than 450ms
• Serum alanine transaminase or aspartate transaminase over 3 times the upper limit of normal, or Child-Pugh class C
• Allergy to amiodarone

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

Sponsors

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew JE Seely, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Ottawa Hospital

Locations

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Andrew JE Seely, MD, PhD

Role: CONTACT

aseely@ohri.ca

613-737-8899 ext. 74052

Facility Contacts

Andrew JE Seely, MD, PhD, FRCSC

Role: primary

aseely@ohri.ca

613-737-8899 ext. 74052

References

Smith HA, Kanji S, Tran DTT, Redpath C, Ferguson D, Lenet T, Sigler G, Gilbert S, Maziak D, Villeneuve P, Sundaresan S, Seely AJE. Prophylaxis for patients at Risk to Eliminate Post-operative Atrial Fibrillation (PREP-AF trial): a protocol for a feasibility randomized controlled study. Trials. 2021 Jun 7;22(1):384. doi: 10.1186/s13063-021-05318-1.

Reference Type: DERIVED

PMID: 34098992 (View on PubMed)

Other Identifiers

20190583-01H

Identifier Type: -

Identifier Source: org_study_id