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

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06067438
• Other study ID #: STUDY00021572
• Secondary ID: NCI-2023-03642ST
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2024
• Est. completion date: August 30, 2025

Study information

• Verified date: June 2024
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Esophageal Carcinoma
• Esophageal Neoplasms

Intervention

Drug:
• Amiodarone Hydrochloride
Given IV and via feeding tube

Other:
• Saline
Given IV

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to AF	Analysis: Log-rank test.	From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 7
Secondary	Serum amiodarone level, classified as therapeutic or subtherapeutic		Post-operative day (POD) 2 to post-operative day (POD) 3