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

NCT04392921 | Unknown DMC

• 1 other identifier: 20190583-01H
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (8)

• Capability for enrolment

  Capacity for enrolment will be assessed, in order to determine recruitment potential and an optimal sample size estimated for a full-scale RCT, by measuring the following outcomes: proportion of patients risk stratified and screened, proportion of eligible individuals consenting to involvement in the study, proportion of recruited individuals who are enrolled in the study.

  Upon study completion, 1 year following study initiation

• Proportion of patients randomized who receive the intervention

  Feasibility of the randomization process will be evaluated including the proportion of patients randomized who receive the intervention

  Upon study completion, 1 year following study initiation

• Knowledge of which patients received intervention and placebo

  Feasibility of blinding of participant, care provider, investigator, and outcomes assessor to the intervention allocation of participants will be evaluated by administering a survey to assess their knowledge of which patients received the intervention and placebo

  Upon study completion, 1 year following study initiation

• Intervention delivery

  Intervention delivery will be assessed by determining if protocol adherence rates exceed \>90% and recording observational data on the quality of intervention delivery using a data collection sheet

  Upon study completion, 1 year following study initiation

• Protocol compliance

  Monitoring of protocol compliance will be measured by the frequency, rate, and rationale of events when study activities diverge from the REB-approved protocol

  Upon study completion, 1 year following study initiation

• Adherence to safety protocol

  Monitoring of safety will be assessed by determining the rate and efficiency of reporting adverse events if they occur and monitoring adherence rates to safety and monitoring protocols

  Upon study completion, 1 year following study initiation

• Proportion of patients for which data could be abstracted

  Feasibility of data extraction analysis will be evaluated by the proportion of patients for which the required data could be abstracted: medication use, incidence of post-operative atrial fibrillation, post-operative outcomes, etc.

  Upon study completion, 1 year following study initiation

• Resources

  Resources required to conduct a future multi-centre PREP-AF trial will be assessed by evaluating the administrative capacity of the POAF research team, including the required number of hours of research assistant time, as well as the feasibility of the designated study budget

  Upon study completion, 1 year following study initiation

Secondary Outcomes (4)

• Incidence of postoperative atrial fibrillation

  Within 30 days post-surgery

• Severity of postoperative atrial fibrillation

  Within 30 days post-surgery

• Hospital length of stay

  Within 30 days post-surgery

• Other postoperative complications

  Within 30 days post-surgery

Study Arms (2)

Intervention Arm

EXPERIMENTAL

Patients randomized to amiodarone treatment

Drug: Amiodarone

Control Arm

PLACEBO COMPARATOR

Patients randomized to placebo treatment

Drug: Placebo

Interventions

Amiodarone 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).

Intervention Arm

Placebo 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).

Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Related Publications (1)

• 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.

  PMID: 34098992 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Amiodarone

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andrew JE Seely, MD, PhD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew JE Seely, MD, PhD

CONTACT

613-737-8899; aseely@ohri.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, single-centre, double arm pragmatic randomized controlled feasibility trial

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 19, 2020
• Study Start: March 7, 2022
• Primary Completion: March 1, 2024
• Study Completion: April 1, 2024
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)