Amiodarone for the Prevention of Atrial Fibrillation After Minimally Invasive Esophagectomy in Patients With Esophageal Cancer

A Prospective, Randomized Controlled Trial Evaluating the Efficacy of Amiodarone in the Prevention of Postoperative Atrial Fibrillation in Patients Undergoing Minimally Invasive Esophagectomy

This phase II trial studies how well amiodarone works in the prevention of atrial fibrillation (AF) after a minimally invasive esophagectomy (MIE) in patients with esophageal cancer. Atrial fibrillation (AF) is an irregular heart rhythm, usually associated with a rapid rate, that is caused by abnormal electrical activity within the atria. AF is the most common complication after MIE for esophageal cancer. There has never been a study of AF after MIE that has used unbiased assignment of patients to receive preventative amiodarone or not. Further, there is no standard recommendation or guideline for preventative medications, such as amiodarone, to decrease the risk of AF in patients having MIE performed for cancer. In fact, most medical centers in the United States and around the world do not give preventative amiodarone after esophagectomy. Giving amiodarone after MIE surgery may be able to reduce the risk of AF for patients with esophageal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation; Esophageal Carcinoma
• Intervention / Treatment: Other: Saline; Drug: Amiodarone Hydrochloride

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the effect of prophylactic amiodarone on the rate of atrial fibrillation (AF) in patients undergoing minimally invasive esophagectomy (MIE).

SECONDARY OBJECTIVES:

I. In each subobjective, below, evaluations of the effects of prophylactic amiodarone on the following will be made:

• Ia. Postoperative (PostOp) rapid ventricular response;
• Ib. Postop pulmonary complications;
• Ic. Postop anastomotic leak;
• Id. Intensive care unit (ICU) readmission;
• Ie. ICU length of stay (LOS);
• If. Hospital LOS;
• Ig. 30-day readmission;
• Ih. Inpatient mortality;
• Ii. 30-day mortality;
• Ij. Adverse events;
• Ik. Time to AF;

Il. Evaluating the association between therapeutic (or serum levels and the development of AF in the experimental group only.

EXPLORATORY OBJECTIVE:

I. To evaluate the effect of prophylactic amiodarone administration on hospital cost of care.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive amiodarone hydrochloride intravenously (IV) for 4 days and then via a feeding tube for 3 days on study.

ARM II: Patients receive placebo (normal saline) IV for 4 days on study.

Patients are followed for 60 days following discharge from hospitalization after MIE.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute
      • Contact: Stephanie Wood; Phone Number: 503-494-6900; Email: woodste@ohsu.edu
      • Principal Investigator: Stephanie Wood

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All patients undergoing MIE will be evaluated for potential enrollment

  • Indication of cancer, esophageal dysplasia or esophageal dysmotilities
• Age > 18 years
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• History of chronic or paroxysmal AF, or atrial flutter
• Previous severe adverse reaction or contraindication to amiodarone (e.g., pulmonary toxicity/fibrosis, hepatotoxicity, thyroid dysfunction)
• Current preoperative use of amiodarone, as baseline home medication
• Development of AF intraoperatively

• Pregnancy

  • Negative pregnancy tests are required for participants of childbearing potential (PCBP) on Day of Surgery (DOS)
• Breastfeeding/chest feeding
• Aborted MIE operation
• QTcB (Bazzett formula) > 500 for heart rate (HR) 60-100 within 30 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (amiodarone hydrochloride); Patients receive amiodarone hydrochloride IV for 4 days and then via a feeding tube for 3 days on study.	Drug: Amiodarone Hydrochloride; Given IV and via feeding tube; Other Names: Cordarone; Nexterone
Placebo Comparator: Arm II (normal saline); Patients receive normal saline IV for 4 days on study.	Other: Saline; Given IV; Other Names: Sodium Chloride 0.9%; ISOTONIC SODIUM CHLORIDE SOLUTION

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of atrial fibrillation (AF), or completion of seven-day course of amiodarone	Will be a binary variable (yes/no) and analyzed using a one-sided test of two proportions at an alpha level of 0.05.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 7, after last dose of enteral amiodarone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative (PostOp) rapid ventricular response	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% confidence interval (CI) of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to discharge (DC) from hospital.
Postop pulmonary complications	Including pneumonia, acute respiratory distress syndrome, acute pulmonary edema, and chylothorax. Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
Anastomotic leak	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
ICU Readmission	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
ICU length of stay (LOS)	Will be assessed in days. Analysis: Wilcoxon rank sum test	From initiation of amiodarone in the intensive care unit (ICU) to time patient is moved out of ICU
Hospital LOS	Will be assessed in days. Analysis: Wilcoxon rank sum test	From initiation of amiodarone in the intensive care unit (ICU) to time of discharge from hospital
30 Day readmission rate	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	Day of discharge (DC) from hospital to 30 days after discharge
Inpatient morality	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to time of discharge from hospital
Incidence of mortality within 30 days of surgery	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
Incidence and type of adverse events	Will be a binary value (yes/no). Analysis: Binomial test; point estimate and 95% CI of the difference between the two proportions.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
Time to AF	Analysis: Log-rank test.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 7
Serum amiodarone level, classified as therapeutic or subtherapeutic		Post-operative day (POD) 2 to post-operative day (POD) 3

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Investigators: Principal Investigator: Stephanie Wood, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): August 30, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: September 28, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Arrhythmias, Cardiac; Esophageal Diseases; Atrial Fibrillation; Esophageal Neoplasms; 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: STUDY00021572 (Other Identifier: OHSU Knight Cancer Institute); NCI-2023-03642 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

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