Atrial Fibrillation, Esophagectomy
Conditions
Keywords
Amiodarone, Atrial fibrillation, Surgical procedures, thoracic
Brief summary
The investigators hypothesize that the medication amiodarone decreases the incidence of atrial fibrillation (AF) following esophagectomy surgery. Their specific aims are to: Determine the effectiveness of amiodarone for the prevention of AF following esophagectomy surgery; Determine the influence of the prevention of AF following esophagectomy surgery on post-surgical duration of stay in the Intensive Care Unit ICU)and duration of post-surgical hospital stay; and Determine the safety of amiodarone for the prevention of AF following esophagectomy surgery.
Detailed description
Thousands of patients undergo major esophagectomy surgery in the United States each year, during which all or a portion of the esophagus is removed. A major complication of these surgeries is the occurrence of an irregular heartbeat known as atrial fibrillation (AF), which develops in up to 40% of patients undergoing these procedures. AF is characterized by rapid, irregular, chaotic beating of the two smaller chambers of the heart (the atria), leading to rapid, irregular beating of the two larger chambers (the ventricles). The average time to occurrence of post-surgical AF is 2-3 days following surgery. AF occurring following esophagectomy can result in extremely rapid heart rates, as fast as 150-200 beats per minute, and may be associated with serious consequences, including severely low blood pressure and potentially debilitating stroke. Further, the risk of death following esophagectomy is significantly higher in patients who develop AF compared with those who do not. Therefore, the occurrence of this irregular heartbeat following esophagectomy is associated with severe, potentially life-threatening consequences. Prevention of this irregular heartbeat in these patients may therefore be very important. Amiodarone is a medication that is known to be effective for prevention and treatment of AF that occurs in patients who have not undergone surgery. In addition, amiodarone has been shown to be effective for prevention of AF following open-chest heart surgery. However, the use of medications for prevention of AF following esophagectomy has not been well studied, and amiodarone has not been studied in a controlled trial for the prevention of AF in this population. In addition, amiodarone is associated with side effects, and it is important to determine the safety of this medication when used in this patient population.
Interventions
DRUGAmiodarone
Intravenous amiodarone continuous infusion x 4 days
OTHERControl
No amiodarone
Sponsors
Purdue University
Indiana University Health
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females over the age of 40 * Scheduled to undergo esophagectomy
Exclusion criteria
* History of atrial fibrillation * Prior severe side effects from amiodarone * Elevated liver enzymes \>3 times the upper limit of normal (UNL) * Corrected QT interval \> 450 ms * Receiving class Ia or class III antiarrhythmics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Atrial Fibrillation | 7 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Post-surgical Hospital Stay | Duration of hospitalization | — |
| Length of Post-surgical Intensive Care Unit Stay | 7 days | — |
| Number of Participants With Adverse Effects | 7 days | Adverse effects, including cardiovascular (hypotension, bradycardia, prolonged QT interval, ventricular tachycardia), respiratory (ARDS, pneumonia, atelectasis), and other (pericardial effusions, anastomotic leak) |
Countries
United States
Participant flow
Recruitment details
Between September 2004 and November 2008, 80 patients were enrolled in the study, with 40 patients randomized to each arm. Patients were recruited from an academic medical center prior to undergoing esophageal surgery
Pre-assignment details
133 patients were screened for eligibility. 39 were excluded prior to consent d/t presence of exclusion criteria or declined participation. 94 were consented. 14 did not participate: 3 had pre-op exclusion criteria; 4 were withdrawn because the study protocol was delayed; 7 were excluded because they developed intra-operative atrial fibrillation
Participants by arm
| Arm | Count |
|---|---|
| Amiodarone Intravenous amiodarone | 40 |
| Control Control usual care | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Control | Amiodarone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 18 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 22 Participants | 43 Participants |
| Age Continuous | 63 years STANDARD_DEVIATION 9 | 61 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 33 Participants | 34 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 40 | 1 / 40 |
| serious Total, serious adverse events | 0 / 40 | 2 / 40 |
Outcome results
Primary
Incidence of Atrial Fibrillation
Time frame: 7 days
Population: Analysis was per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone | Incidence of Atrial Fibrillation | 6 participants |
| Control | Incidence of Atrial Fibrillation | 16 participants |
p-value: 0.0295% CI: [0.16, 0.86]Chi-squared
Secondary
Length of Post-surgical Hospital Stay
Time frame: Duration of hospitalization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amiodarone | Length of Post-surgical Hospital Stay | 11 days |
| Control | Length of Post-surgical Hospital Stay | 12 days |
p-value: 0.31Wilcoxon (Mann-Whitney)
Secondary
Length of Post-surgical Intensive Care Unit Stay
Time frame: 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amiodarone | Length of Post-surgical Intensive Care Unit Stay | 68 hours |
| Control | Length of Post-surgical Intensive Care Unit Stay | 77 hours |
p-value: 0.097Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Adverse Effects
Adverse effects, including cardiovascular (hypotension, bradycardia, prolonged QT interval, ventricular tachycardia), respiratory (ARDS, pneumonia, atelectasis), and other (pericardial effusions, anastomotic leak)
Time frame: 7 days
Population: Per protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amiodarone | Number of Participants With Adverse Effects | 21 patients |
| Control | Number of Participants With Adverse Effects | 19 patients |
p-value: 0.66Chi-squared