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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Atrial Fibrillation, Esophageal Carcinoma

Intervention / Treatment
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* Drug: Amiodarone Hydrochloride
* Other: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (amiodarone hydrochloride)<br>Patients receive amiodarone hydrochloride IV for 4 days and then via a feeding tube for 3 days on study. | Drug: Amiodarone Hydrochloride<br>* Given IV and via feeding tube<br>* Other names: Nexterone;|
| Placebo Comparator: Arm II (normal saline)<br>Patients receive normal saline IV for 4 days on study. | Other: Saline<br>* Given IV<br>* Other names: Sodium Chloride 0.9%;|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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. |