Evaluating the Effectiveness of Fish Oil Supplements at Reducing the Recurrence of Atrial Fibrillation

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00552084
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), eCardio Diagnostics (Other), GlaxoSmithKline (Industry)
• Enrollment: 190
• Location: 1
• Arms: 2
• Duration (Months): 77
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Atrial fibrillation (AF) is a heart rhythm disorder that usually involves a rapid heart rate. People who take fish oil supplements may reduce the risk of a recurrence of AF. This study will evaluate the effectiveness of fish oil at decreasing the recurrence of AF and will examine the reasons why fish oil may reduce this risk.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Fish oil; Drug: Placebo	Phase 4

Detailed Description

AF is the most common type of serious heart arrhythmia. It affects approximately 2% of the population and is becoming more common. In AF, the heart's atria, or upper chambers, contract in a very disorganized and abnormal manner and are unable to correctly pump blood into the heart's ventricles, or lower chambers. Symptoms may include a rapid or irregular pulse, dizziness, fainting, or breathing difficulty. Recent studies suggest that inflammation plays a fundamental role in the development of AF. Inflammation, and the resulting oxidative stress, can cause cellular and tissue damage. In turn, this may alter heart function, potentially leading to both the onset and recurrence of AF. Markers of inflammation, such as C-reactive protein (CRP) and interleukin-6 (IL-6), are often elevated in patients with AF, providing further evidence of inflammation's role. While there are several treatment options for AF, they are usually only moderately effective. Previous research has shown that fish oil supplements have anti-inflammatory, antifibrotic, and antioxidant effects and can reduce the risk of AF following surgery. However, it is not known exactly how fish oil reduces this risk and whether the same positive effect will carry over in people who experience the more common type of AF that is unrelated to surgery. The purpose of this study is to evaluate the effectiveness of fish oil supplementation at decreasing the recurrence of AF in adults who have not undergone recent surgery. Researchers will also examine the ways in which fish oil reduces AF recurrence.

This study will enroll people who have had at least two occurrences of AF. Participants will be randomly assigned to receive either fish oil supplements or placebo for 24 weeks. At study visits at baseline and Weeks 2, 4, 8, 12, 18, and 24, participants will undergo a medical and social history review, a physical exam, and blood and urine collection. At the baseline study visit, an electrocardiogram will also occur.

Study Design

• Study Type: Interventional
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fish Oil for Atrial Fibrillation - Effect and Mechanisms
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fish Oil 4 grams fish oil daily for 24 weeks	Drug: Fish oil; Fish oil supplements 4 gms will be taken daily for 24 weeks.; Other Names: Lovaza capsule (1 gm)containing 465 mg EPA and 375 mg DHA.
Placebo Comparator: Placebo corn oil taken daily for 24 weeks	Drug: Placebo; Placebo supplements will be taken daily for 24 weeks.; Other Names: Corn oil

Outcome Measures

Primary Outcome Measures

1. Documented Recurrence of Atrial Fibrillation/Atrial Flutter [Measured at Week 24 or exit]

   Trans-telephonic electrocardiographic monitoring (TTM) device were used to send transmissions every 2 weeks and each time a participant had symptoms suggestive of arrhythmia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• =21 years of age

• a history of atrial fibrillation

• a history of at least two occurrences of atrial fibrillation or atrial flutter, at least one of which is atrial fibrillation

• an electrocardiogram that was recorded within 12 months of randomization showing atrial fibrillation or atrial flutter

• sinus rhythm at the time the first dose of randomized medication is taken

• stable antiarrhythmic medications

• if the patient has had an ablation for atrial fibrillation or flutter or a MAZE procedure, the qualifying episode of atrial fibrillation must have occurred at least 3 months post-procedure

• normal serum potassium level within the last 28 days

• provided informed consent

Exclusion Criteria:

• permanent atrial fibrillation or flutter

• New York Heart Association class III or IV heart failure or Canadian Cardiovascular Society class III or IV angina pectoris

• cardiac or thoracic surgery within the previous 3 months

• acute pericarditis within the previous 3 months

• other reversible causes of atrial fibrillation such as thyrotoxicosis

• acute myocardial infarction or unstable angina within the previous 3 months

• history of neurologic event (TIA or stroke)within the past 3 months

• history of acute congestive heart failure precipitated by atrial fibrillation, and the patient is not receiving rate-control therapy

• Wolff-Parkinson-White syndrome

• a medical condition that is likely to be fatal in less than one year

• active, uncontrolled co-morbid inflammatory condition (e.g., rheumatoid arthritis, inflammatory bowel disease, SLE)

• receiving cytotoxic chemotherapy or radiotherapy for cancer

• taking a fish oil supplement

• allergic to fish

• bleeding event not related to trauma or surgery requiring hospitalization or transfusion in previous year

• systolic blood pressure < 90 mm Hg or heart rate <50 beats/minute

• history of ventricular fibrillation or sustained ventricular tachycardia, or presence of an implanted defibrillator placed for the occurrence of such an event or the presence of an Implantable Cardioverter-Defibrillator (ICD) that has discharged appropriately for a ventricular arrhythmia

• pregnant or breast feeding

• enrollment in another research study involving an intervention

• on dialysis or recipient of a renal transplant

• use of potentially cardiotoxic illegal drugs (cocaine, methamphetamine, opioids) in the last 12 months

• Treated for alcoholism and currently drinking alcohol to excess or alcoholic cardiomyopathy as the primary clinical diagnosis and currently drinking alcohol to excess

• presence of an iron-storage disease, such as hemochromatosis, transfusional hemosiderosis, or those subjects in whom a daily dose of up to 20 mg elemental iron (in and of itself or in addition of current iron supplementation) would post a risk for toxicity from iron overload

• subjects receiving or anticipated to receive intravenous iron therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt Medical School	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University
• National Heart, Lung, and Blood Institute (NHLBI)
• eCardio Diagnostics
• GlaxoSmithKline

Investigators

• Principal Investigator: Charles M. Stein, Vanderbilt Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: C. Michael Stein, Dan May Professor of Medicine, Professor of Pharmacology, Assistant Director of the Division of Clinical Pharmacology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00552084
• Other Study ID Numbers: 543; R01HL087254; HL 087254
• First Posted: Nov 1, 2007
• Last Update Posted: Dec 3, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by C. Michael Stein, Dan May Professor of Medicine, Professor of Pharmacology, Assistant Director of the Division of Clinical Pharmacology, Vanderbilt University: Fish Oil
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 4 medical centers in Nashville Tennessee, and at the Marsh field Clinic in Madison, Wisconsin. Between December 2007 and December 2012, 241 patients were enrolled and 190 (178 at Vanderbilt, 12 at other sites) were randomized to fish oil (126) or placebo (64). Of 190 enrolled, 173 (91%) completed the study.
Pre-assignment Detail	Patients were >= 21 years old with a history of at least 2 occurrences of atrial fibrillation or atrial flutter, and in sinus rhythm at randomization. Randomization was performed according to a computer-generated block scheme according to anti-arrhythmic therapy: 1. no therapy, 2. amiodarone, 3. class 1 anti-arrhythmic drugs, 4.sotalol/dofetilide.

Arm/Group Title	Fish Oil	Placebo
Arm/Group Description	4 grams fish oil daily for 24 weeks Fish oil: Fish oil supplements 4 gms will be taken daily for 24 weeks.	corn oil taken daily for 24 weeks Placebo: Placebo supplements will be taken daily for 24 weeks.
Period Title: Overall Study
STARTED	126	64
COMPLETED	118	55
NOT COMPLETED	8	9

Baseline Characteristics

Arm/Group Title	Fish Oil	Placebo	Total
Arm/Group Description	4 grams fish oil daily for 24 weeks Fish oil: Fish oil supplements 4 gms will be taken daily for 24 weeks.	corn oil taken daily for 24 weeks Placebo: Placebo supplements will be taken daily for 24 weeks.	Total of all reporting groups
Overall Participants	126	64	190
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61.9	61.5	61.7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	62 49.2%	38 59.4%	100 52.6%
>=65 years	64 50.8%	26 40.6%	90 47.4%
Sex: Female, Male (Count of Participants)
Female	59 46.8%	22 34.4%	81 42.6%
Male	67 53.2%	42 65.6%	109 57.4%
Region of Enrollment (participants) [Number]
United States	126 100%	64 100%	190 100%

Outcome Measures

1. Primary Outcome

Title	Documented Recurrence of Atrial Fibrillation/Atrial Flutter
Description	Trans-telephonic electrocardiographic monitoring (TTM) device were used to send transmissions every 2 weeks and each time a participant had symptoms suggestive of arrhythmia.
Time Frame	Measured at Week 24 or exit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fish Oil	Placebo
Arm/Group Description	4 grams fish oil daily for 24 weeks Fish oil: Fish oil supplements 4 gms will be taken daily for 24 weeks.	corn oil taken daily for 24 weeks Placebo: Placebo supplements will be taken daily for 24 weeks.
Measure Participants	126	64
Number [percentage of participants]	59 46.8%	47 73.4%

Adverse Events

Time Frame	Adverse event data were collected during the 24 week study, after participants took first dose of study medication or placebo.
Arm/Group Title	Fish Oil		Placebo
Arm/Group Description	4 grams fish oil daily for 24 weeks Fish oil: Fish oil supplements 4 gms will be taken daily for 24 weeks.		corn oil taken daily for 24 weeks Placebo: Placebo supplements will be taken daily for 24 weeks.
All Cause Mortality
	Fish Oil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fish Oil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/126 (1.6%)		3/64 (4.7%)
Cardiac disorders
acute coronary syndrome	0/126 (0%)	0	1/64 (1.6%)	1
bradycardia	0/126 (0%)	0	1/64 (1.6%)	1
rapid atrial fibrillation	0/126 (0%)	0	1/64 (1.6%)	1
General disorders
non-cardiac chest pain	1/126 (0.8%)	1	0/64 (0%)	0
Musculoskeletal and connective tissue disorders
pseudogout	1/126 (0.8%)	1	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	Fish Oil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/126 (31.7%)		13/64 (20.3%)
Blood and lymphatic system disorders
Low INR	17/126 (13.5%)		2/64 (3.1%)
Gastrointestinal disorders
Diarrhea	6/126 (4.8%)		1/64 (1.6%)
Nausea	6/126 (4.8%)		2/64 (3.1%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection	11/126 (8.7%)		8/64 (12.5%)

Limitations/Caveats

We determined recurrence of Atrial Fibrillation(AF) by both routine and symptomatic TTM transmissions. We did not examine the effect of therapy on total AF burden. Sample size was relatively small, and included a heterogeneous patient population.

More Information

Certain Agreements

All Principal Investigators ARE 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.