Clinical trial NCT06067438: Amiodarone for the Prevention of Atrial Fibrillation After Minimally Invasive Esophagectomy in Patients With Esophageal Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Atrial Fibrillation
Esophageal Carcinoma
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
First posted: 2023-10-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo (normal saline) IV for 4 days in the absence of disease progression or unacceptable toxicity.

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

Eligibility criteria: 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
* QTcF (Fridericia formula) \> 500 for heart rate (HR) 60-100 within 30 days

  * For patients with a heart rate (HR) of between 50-59 on their pre-operative screening electrocardiography (EKG), we will first review evidence of chronotropic cardiac response to exercise before inclusion in the study. If a patient's HR increases to ≥ 100 with exercise, the patient is eligible for inclusion of study. Exercise testing options may include a stair climb, a brisk walk, or supine leg-lifts prior to surgery. If exercise is not an option, we can review results of formal stress testing chronotropic response (ie. HR ≥ 100). HR monitoring can be collected by either pulse oximeter or EKG

Primary outcomes:
measure: Development of atrial fibrillation (AF), or completion of seven-day course of amiodarone
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 7, after last dose of enteral amiodarone
Secondary outcomes:
measure: Postoperative (PostOp) rapid ventricular response
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to discharge (DC) from hospital.
measure: Postop pulmonary complications
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
measure: Anastomotic leak
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
measure: ICU Readmission
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
measure: ICU length of stay (LOS)
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to time patient is moved out of ICU
measure: Hospital LOS
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to time of discharge from hospital
measure: 30 Day readmission rate
timeFrame: Day of discharge (DC) from hospital to 30 days after discharge
measure: Inpatient morality
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to time of discharge from hospital
measure: Incidence of mortality within 30 days of surgery
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
measure: Incidence and type of adverse events
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 30
measure: Time to AF
timeFrame: From initiation of amiodarone in the intensive care unit (ICU) to post-operative day (POD) 7
measure: Serum amiodarone level, classified as therapeutic or subtherapeutic
timeFrame: Post-operative day (POD) 2 to post-operative day (POD) 3
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Stephanie Wood
role: PRINCIPAL_INVESTIGATOR
References: