Heart Failure
Conditions
Brief summary
This study will examine whether an intervention with vitamin D or fish oil supplements can reduce the risk of heart failure among adult men and women during a follow up period of up to five years (starting from the time of randomization into the parent VITAL trial). The investigators hypotheses are that both vitamin D and fish oil supplements will each reduce the risk of heart failure.
Detailed description
For this ancillary study of the ongoing parent VITAL trial, we will adjudicate incident heart failure cases occurring during a time period of up to five years starting from randomization of subjects in the parent VITAL study. Intention-to-treat analysis will be used to assess the efficacy of vitamin D as well as omega-3 fatty acids.
Interventions
2000 IU vitamin D and 1g/d fish oil
DIETARY_SUPPLEMENTFish oil (EPA/DHA) alone
1 g/d fish oil
DRUGVitamin D alone
2000 IU vitamin D
OTHERPlacebo
Vitamin D placebo and fish oil placebo
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men aged 50 or older or women aged 55 or older * Be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D \[e.g., Fosamax Plus D\], and multivitamins), or, if taking, willing to decrease or forego such use during the trial; * Be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial; * Not be taking fish oil supplements, or, if taking, willing to forego their use during the trial
Exclusion criteria
* prevalent heart failure * History of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, CABG, or PCI * History of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or Wegener's granulomatosis; * Allergy to fish or soy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With New Heart Failure Hospitalization | 5 years | We will consider any hospitalization for heart failure among participants enrolled in the parent VITAL trial for this ancillary study. Incident heart failure are initially captured through annual questionnaires with subsequent validation by a team of physicians with expertise in cardiovascular medicine and epidemiology. We excluded 36 participants with prevalent heart failure at the time of randomization for the primary analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Recurrent Heart Failure Hospitalization | 5 years | Recurrent heart failure hospitalizations ascertained either by review of medical records and/or use of CMS (Center for Medicare and Medicaid Services) data. |
Countries
United States
Participant flow
Recruitment details
A total of 401605 adults were initially screened; 39430 eligible to enter run-in; 25871 eligible for randomization; 2x2 factorial design: 12927 assigned to active vit D (of these, 6463 were assigned to active omega-3 FAs and 6464 to placebo omega-3 FAs) & 12944 assigned to placebo vit D (of these, 6470 were assigned to active omega-3 FAs and 6474 to placebo omega-3 FAs)
Pre-assignment details
The trial included a 3-month placebo run-in period to select participants likely to have excellent compliance. Only individuals who reported taking at least 2/3 of their study pills during the run-in and met other eligibility criteria were randomized into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Active Vitamin D + Active Omega-3 Fatty Acids Active Vitamin D = Vitamin D3, one 2000 IU capsule/day; Active Omega-3 Fatty Acids = Omacor, one 1-gram capsule/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 \[DHA\]). | 6,463 |
| Active Vitamin D + Placebo Omega-3 Fatty Acids Active Vitamin D = Vitamin D3, one 2000 IU capsule/day; Placebo Omega-3 Fatty Acids, one capsule/day | 6,464 |
| Placebo Vitamin D + Active Omega-3 Fatty Acids Placebo Vitamin D, one capsule/day; Active Omega-3 Fatty Acids = Omacor, one 1-gram capsule/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 \[DHA\]). | 6,470 |
| Placebo Vitamin D + Placebo Omega-3 Fatty Acids Placebo Vitamin D, one capsule/day; Placebo Omega-3 Fatty Acids, one capsule/day | 6,474 |
| Total | 25,871 |
Baseline characteristics
| Characteristic | Active Vitamin D + Active Omega-3 Fatty Acids | Active Vitamin D + Placebo Omega-3 Fatty Acids | Placebo Vitamin D + Active Omega-3 Fatty Acids | Placebo Vitamin D + Placebo Omega-3 Fatty Acids | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7 | 67.2 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized count African American | 1278 Participants | 1275 Participants | 1271 Participants | 1282 Participants | 5106 Participants |
| Race/Ethnicity, Customized count Asian/Pacific Islander | 102 Participants | 86 Participants | 98 Participants | 102 Participants | 388 Participants |
| Race/Ethnicity, Customized count Hispanic (not African American) | 246 Participants | 270 Participants | 245 Participants | 252 Participants | 1013 Participants |
| Race/Ethnicity, Customized count Native American/Alaskan Native | 62 Participants | 56 Participants | 58 Participants | 52 Participants | 228 Participants |
| Race/Ethnicity, Customized count Non-Hispanic White | 4515 Participants | 4498 Participants | 4529 Participants | 4504 Participants | 18046 Participants |
| Race/Ethnicity, Customized count Other/Unknown | 126 Participants | 133 Participants | 123 Participants | 141 Participants | 523 Participants |
| Region of Enrollment United States | 6463 participants | 6464 participants | 6470 participants | 6474 participants | 25871 participants |
| Sex: Female, Male Female | 3276 Participants | 3271 Participants | 3271 Participants | 3267 Participants | 13085 Participants |
| Sex: Female, Male Male | 3187 Participants | 3193 Participants | 3199 Participants | 3207 Participants | 12786 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 485 / 12,927 | 493 / 12,944 | 493 / 12,933 | 485 / 12,938 |
| other Total, other adverse events | 10,086 / 12,927 | 10,098 / 12,944 | 10,094 / 12,933 | 10,090 / 12,938 |
| serious Total, serious adverse events | 1,673 / 12,927 | 1,659 / 12,944 | 1,613 / 12,933 | 1,619 / 12,938 |
Outcome results
Primary
Number of Participants With New Heart Failure Hospitalization
We will consider any hospitalization for heart failure among participants enrolled in the parent VITAL trial for this ancillary study. Incident heart failure are initially captured through annual questionnaires with subsequent validation by a team of physicians with expertise in cardiovascular medicine and epidemiology. We excluded 36 participants with prevalent heart failure at the time of randomization for the primary analysis.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Vitamin D | Number of Participants With New Heart Failure Hospitalization | 240 Participants |
| Vitamin D Placebo | Number of Participants With New Heart Failure Hospitalization | 259 Participants |
| Active Omega-3 Fatty Acids | Number of Participants With New Heart Failure Hospitalization | 244 Participants |
| Omega-3 Fatty Acids Placebo | Number of Participants With New Heart Failure Hospitalization | 255 Participants |
95% CI: [0.78, 1.11]
95% CI: [0.8, 1.14]
Secondary
Number of Recurrent Heart Failure Hospitalization
Recurrent heart failure hospitalizations ascertained either by review of medical records and/or use of CMS (Center for Medicare and Medicaid Services) data.
Time frame: 5 years
Population: Each participant is allowed to have multiple heart failure hospitalizations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Vitamin D | Number of Recurrent Heart Failure Hospitalization | 341 hospitalizations for heart failure |
| Vitamin D Placebo | Number of Recurrent Heart Failure Hospitalization | 364 hospitalizations for heart failure |
| Active Omega-3 Fatty Acids | Number of Recurrent Heart Failure Hospitalization | 326 hospitalizations for heart failure |
| Omega-3 Fatty Acids Placebo | Number of Recurrent Heart Failure Hospitalization | 379 hospitalizations for heart failure |
95% CI: [0.81, 1.09]
95% CI: [0.74, 0.998]