Prevention of Atrial Fibrillation Following Esophagectomy

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00420017
• Collaborator: Purdue University (Other), Indiana University Health (Other)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Esophagectomy	Drug: Amiodarone; Other: Control	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prevention of Atrial Fibrillation Following Thoracoabdominal Esophagectomy Surgery
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amiodarone Intravenous amiodarone	Drug: Amiodarone; Intravenous amiodarone continuous infusion x 4 days
Other: Control Control	Other: Control; No amiodarone

Outcome Measures

Primary Outcome Measures

1. Incidence of Atrial Fibrillation [7 days]

Secondary Outcome Measures

1. Length of Post-surgical Hospital Stay [Duration of hospitalization]

2. Length of Post-surgical Intensive Care Unit Stay [7 days]

3. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Hospital	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University
• Purdue University
• Indiana University Health

Investigators

• Principal Investigator: James E Tisdale, PharmD, Purdue University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: James E. Tisdale, Professor and Interim Head, Department of Pharmacy Practice, Purdue University, and Adjunct Professor, School of Medicine, Indiana University, Purdue University
• ClinicalTrials.gov Identifier: NCT00420017
• Other Study ID Numbers: 0510-23
• First Posted: Jan 9, 2007
• Last Update Posted: Sep 18, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by James E. Tisdale, Professor and Interim Head, Department of Pharmacy Practice, Purdue University, and Adjunct Professor, School of Medicine, Indiana University, Purdue University: Amiodarone; Atrial fibrillation; Surgical procedures, thoracic
• Additional relevant MeSH terms: Atrial Fibrillation; Amiodarone

Study Results

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 Detail	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

Arm/Group Title	Amiodarone	Control
Arm/Group Description	Intravenous amiodarone	Control usual care
Period Title: Overall Study
STARTED	40	40
COMPLETED	38	40
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Amiodarone	Control	Total
Arm/Group Description	Intravenous amiodarone	Control usual care	Total of all reporting groups
Overall Participants	40	40	80
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	22 55%	21 52.5%	43 53.8%
>=65 years	18 45%	19 47.5%	37 46.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61 (10)	63 (9)	62 (9.5)
Sex: Female, Male (Count of Participants)
Female	6 15%	7 17.5%	13 16.3%
Male	34 85%	33 82.5%	67 83.8%
Region of Enrollment (participants) [Number]
United States	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Atrial Fibrillation
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Analysis was per protocol

Arm/Group Title	Amiodarone	Control
Arm/Group Description	Intravenous amiodarone	Control usual care
Measure Participants	40	40
Number [participants]	6 15%	16 40%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amiodarone, Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Length of Post-surgical Hospital Stay
Time Frame	Duration of hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amiodarone	Control
Arm/Group Description	Intravenous amiodarone	Control usual care
Measure Participants	40	40
Median (Inter-Quartile Range) [days]	11	12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amiodarone, Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Length of Post-surgical Intensive Care Unit Stay
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Amiodarone	Control
Arm/Group Description	Intravenous amiodarone	Control usual care
Measure Participants	40	40
Median (Inter-Quartile Range) [hours]	68	77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amiodarone, Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.097
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Number of Participants With Adverse Effects
Description	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

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Amiodarone	Control
Arm/Group Description	Intravenous amiodarone	Control usual care
Measure Participants	40	40
Number [patients]	21	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Amiodarone, Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Arm/Group Title	Amiodarone		Control
Arm/Group Description	Intravenous amiodarone		Control usual care
All Cause Mortality
	Amiodarone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Amiodarone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		2/40 (5%)
General disorders
death	0/40 (0%)	0	2/40 (5%)	2
Other (Not Including Serious) Adverse Events
	Amiodarone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/40 (7.5%)		1/40 (2.5%)
Cardiac disorders
bradycardia	3/40 (7.5%)	3	1/40 (2.5%)	1

Limitations/Caveats

Design not double-blind placebo-control Atrial fibrillation was left to discretion of treating MD Larger study necessary to determine differences in length of hospital stay and cost and identify infrequently occurring amiodarone adverse effects

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.