Atrial Fibrillation
Conditions
Keywords
Fish Oil
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.
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.
Interventions
DRUGFish oil
Fish oil supplements 4 gms will be taken daily for 24 weeks.
DRUGPlacebo
Placebo supplements will be taken daily for 24 weeks.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
eCardio Diagnostics
GlaxoSmithKline
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Fish Oil 4 grams fish oil daily for 24 weeks
Fish oil: Fish oil supplements 4 gms will be taken daily for 24 weeks. | 126 |
| Placebo corn oil taken daily for 24 weeks
Placebo: Placebo supplements will be taken daily for 24 weeks. | 64 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | change in anti-arrythmic drug | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Fish Oil | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 64 Participants | 26 Participants | 90 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 38 Participants | 100 Participants |
| Age, Continuous | 61.9 years | 61.5 years | 61.7 years |
| Region of Enrollment United States | 126 participants | 64 participants | 190 participants |
| Sex: Female, Male Female | 59 Participants | 22 Participants | 81 Participants |
| Sex: Female, Male Male | 67 Participants | 42 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 126 | 13 / 64 |
| serious Total, serious adverse events | 2 / 126 | 3 / 64 |
Outcome results
Primary
Documented Recurrence of Atrial Fibrillation/Atrial Flutter
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fish Oil | Documented Recurrence of Atrial Fibrillation/Atrial Flutter | 59 percentage of participants |
| Placebo | Documented Recurrence of Atrial Fibrillation/Atrial Flutter | 47 percentage of participants |