VITAL Rhythm Study

Study Overview
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Brief Summary
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The VITamin D and OmegA-3 TriaL (VITAL) is an ongoing randomized clinical trial of 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in individuals who do not have a prior history of these illnesses. The purpose of this ancillary study is to ascertain and adjudicate atrial fibrillation (AF) outcomes for the primary aim of testing whether omega-3 fatty acid and/or vitamin D supplementation influence atrial fibrillation risk in the general population. We also plan to examine how these agents might impact the development of AF subtypes (persistent versus paroxysmal), intermediate phenotypes for heart rhythm disorders (electrocardiographic parameters), as well as explore effects on arrhythmic death and whether baseline blood levels and/or race modify treatment effects.

Detailed Description
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Atrial fibrillation and sudden cardiac death assessments, as well as blood analyses, will be conducted on the entire VITAL Study population, and ECG analyses will be limited to the Clinical and Translational Science Center (CTSC) sub-cohort of 1,054 VITAL participants who live near the Boston area and agree to participate in a series of ancillary studies in addition to the main trial. Investigators will ascertain atrial fibrillation events utilizing self-report of physician diagnoses of atrial fibrillation received on annual questionnaires from study participants supplemented by outpatient and hospital visits for AF identified through Centers for Medicare and Medicaid Services (CMS) data linkage. Investigators will also ascertain additional information regarding atrial fibrillation diagnosis from supplementary questionnaires, and seek consent to review all inpatient and outpatient hospital records pertaining to atrial fibrillation diagnosis and evaluation. Atrial fibrillation events will be confirmed by an endpoint committee composed of cardiologists, which will also make a determination on atrial fibrillation subtype and pattern. Questionnaires that inquire about recurrent atrial fibrillation events, pattern of AF, latest medical record evaluation and treatments for AF will be sent to participants with confirmed atrial fibrillation. Medical records will be requested and reviewed an endpoint committee to determine atrial fibrillation subtype and progression. An intention-to-treat analysis examining the 5-year treatment effects of omega-3 fatty acids and vitamin D on incident atrial fibrillation, as well as subtypes at the time of diagnosis will be performed to address the primary aims. We will repeat these analyses at the end of extended follow-up to assess cumulative and post-treatment effects of omega-3 fatty acids and vitamin D and AF subtypes two years after diagnosis. Electrocardiograms will be obtained at baseline and again after two years of treatment and follow-up among a sub-cohort of 1,054 patients being enrolled in VITAL at the CTSC. Investigators will utilize these ECG data to evaluate whether treatment with omega-3 fatty acids and vitamin D3 have significant effects on ECG measures. The ECGs will also be utilized to estimate the prevalence of asymptomatic persistent atrial fibrillation in our population not detected by our atrial fibrillation surveillance methods. Investigators will examine baseline blood samples for participants with confirmed atrial fibrillation for the purpose of exploring whether the effect of vitamin D3 or fish oil supplementation on atrial fibrillation risk varies by the baseline blood levels of these nutrients. Investigators will also seek additional information necessary to classify deaths as sudden or arrhythmic in origin, and cardiac deaths will be reviewed by an endpoint committee of cardiologists. Once these results have been compiled investigators will explore whether omega-3 fatty acids and/or vitamin D might have an effect on sudden and/or arrhythmic cardiac death.

Official Title
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Vitamin D and Omega-3 Trial (VITAL Rhythm Study)

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Drug: Omega-3 fatty acids (fish oil)
* Dietary Supplement: Fish oil placebo
* Dietary Supplement: Vitamin D3 placebo


Participation Criteria
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Eligibility Criteria
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To be eligible this ancillary study participants must be enrolled in the Vitamin D and Omega-3 Trial (VITAL; National Clinical Trial (NCT) 01169259) and meet the following criteria: Inclusion Criteria: - physician diagnosis of atrial fibrillation after randomization and/or - cardiovascular death Exclusion Criteria: - physician diagnosis of atrial fibrillation prior to randomization

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D + fish oil<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>* Other names: cholecalciferol;Drug: Omega-3 fatty acids (fish oil)<br>* Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).<br>|
| Active Comparator: Vitamin D + fish oil placebo<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3 (cholecalciferol), 2000 IU per day.<br>* Other names: cholecalciferol;Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>|
| Active Comparator: Vitamin D placebo + fish oil<br> | Drug: Omega-3 fatty acids (fish oil)<br>* Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).<br>Dietary Supplement: Vitamin D3 placebo<br>* Vitamin D3 placebo<br>|
| Placebo Comparator: Vitamin D placebo + fish oil placebo<br> | Dietary Supplement: Fish oil placebo<br>* Fish oil placebo<br>Dietary Supplement: Vitamin D3 placebo<br>* Vitamin D3 placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Fibrillation | To assess whether omega-3 fatty acids (Omacor® 840 mg eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) or vitamin D3 supplementation influences risk of atrial fibrillation in a general population of men and women without prior cardiovascular disease. | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial Fibrillation | To examine the short and long-term impacts of vitamin D3 and EPA+DHA supplementation on the development of AF subtypes. | 7 years | 
| Arrhythmic endpoints | To examine the effect of vitamin D3 or EPA+DHA supplementation on electrocardiographic parameters to further understand mechanisms underlying associations with arrhythmic endpoints. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Vitamin D3, Omega-3 fatty acids, Fish oil