Cancer, Cardiovascular Disease
Conditions
Keywords
vitamin D3, omega-3 fatty acids, fish oil, cardiovascular disease, cancer, primary prevention
Brief summary
The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial in 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 people who do not have a prior history of these illnesses. The 5-year intervention phase (study pill-taking, median 5.3 years) has ended; post-intervention observational follow-up of study participants is ongoing.
Detailed description
The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial of vitamin D (in the form of vitamin D3 \[cholecalciferol\]) and marine omega-3 fatty acid (eicosapentaenoic acid \[EPA\] + docosahexaenoic acid \[DHA\]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Existing data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents may reduce risk for cancer or CVD, but large primary prevention trials with adequate dosing in general populations are lacking. VITAL tested the independent effects of vitamin D and omega-3 fatty acid supplementation on risk for developing cancer and CVD (primary, secondary, and other outcomes are specified in the Outcome Measures section). VITAL also explored (a) whether vitamin D and omega-3 fatty acid supplements exhibit synergistic or additive effects on cancer and CVD risk and (b) whether the effect of each supplement on cancer and CVD risk varies by baseline blood levels or intake of vitamin D and EPA+DHA, race/ethnicity, and body mass index (for vitamin D), as well as age, sex, sunlight exposure, calcium intake, and baseline risk factors for cancer and CVD. Eligible participants were assigned by chance (like a coin toss) to one of four groups: (1) daily vitamin D and omega-3; (2) daily vitamin D and omega-3 placebo; (3) daily vitamin D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants had an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of getting at least one active agent. Participants in all groups took two pills each day -- one softgel that contained either vitamin D or vitamin D placebo and one capsule that contained either omega-3 or omega-3 placebo. Participants received their study pills in convenient calendar packages via U.S. mail. Participants fill out a short (15-20 minute) questionnaire each year. The questionnaire asks about health; lifestyle habits such as physical exercise, diet, and smoking; use of medications and dietary supplements; family history of illness, and new medical diagnoses. We request consent for medical record review to confirm endpoints. Occasionally, participants may receive a phone call from study staff to collect information or to clarify responses on the questionnaire. At baseline, 16,954 VITAL participants provided an optional blood sample. Approximately 6,000 of these participants provided a follow-up blood sample during years 1-5 of the trial. At baseline, year 2, and year 4 of the trial, a subcohort of 1,054 VITAL participants living within driving distance of Boston, Massachusetts received detailed in-clinic health assessments at the Clinical and Translational Science Center (CTSC) of Brigham and Women's Hospital. During CTSC visits, participants had a clinical exam, including measurement of height, weight, other anthropometrics, blood pressure, and physical performance. They also provided fasting blood and urine samples, and underwent 2-hour oral glucose tolerance testing, lung function testing (spirometry), electrocardiograms, bone mineral density testing, 2D-echocardiography, and assessments of thinking and mood. VITAL is supported by funding from the National Cancer Institute, National Heart, Lung and Blood Institute, Office of Dietary Supplements, National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma (BASF) of Norway (Omacor® fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs.
Interventions
DIETARY_SUPPLEMENTvitamin D3
Vitamin D3 (cholecalciferol), 2000 IU per day.
Omacor, one 1-gram 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 \[DHA\]).
DIETARY_SUPPLEMENTVitamin D3 placebo
Vitamin D placebo
DIETARY_SUPPLEMENTFish oil placebo
Fish oil placebo
Sponsors
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Office of Dietary Supplements (ODS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)
Pharmavite LLC
Pronova BioPharma
BASF
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
To be eligible for the study, respondents had to, at study entry,: 1. be men aged 50 or older or women aged 55 or older; 2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, coronary-artery bypass grafting, or percutaneous coronary intervention; 3. have none of the following safety exclusions: 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 granulomatosis with polyangiitis (Wegener's); 4. have no allergy to fish or soy; 5. have no other serious illness that would preclude participation; 6. 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; 7. 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; 8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Invasive Cancer of Any Type | 5 years | Number of participants with invasive cancer of any type |
| Number of Participants With a Major Cardiovascular Event | 5 years | Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died From Invasive Cancer of Any Type | 5 years | Number of participants who died from invasive cancer of any type |
| Number of Female Participants With Breast Cancer | 5 years | Number of female participants with breast cancer |
| Number of Male Participants With Prostate Cancer | 5 years | Number of male participants with prostate cancer |
| Number of Participants With Colorectal Cancer | 5 years | Number of participants with colorectal cancer |
| Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint | 5 years | Expanded composite cardiovascular endpoint = a composite endpoint of myocardial infarction, stroke, death from cardiovascular causes, and coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention) |
| Number of Participants With Myocardial Infarction | 5 years | Number of participants with myocardial infarction |
| Number of Participants With Stroke | 5 years | Number of participants with stroke |
| Number of Participants Who Died From Cardiovascular Causes | 5 years | Number of participants who died from cardiovascular causes |
| Number of Participants Who Died From Any Cause | 5 years | Number of participants who died from any cause |
| Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 5 years, excluding first 2 years of follow-up | Number of participants with invasive cancer of any type, excluding first 2 years of follow-up |
| Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up | 5 years, excluding first 2 years of follow-up | Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes; excluding first 2 years of follow-up |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Coronary-artery Bypass Grafting | 5 years | Number of participants with coronary-artery bypass grafting |
| Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up | 5 years, excluding first 2 years of follow-up | Number of participants who died from any cause, excluding first 2 years of follow-up |
| Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 5 years, excluding first 2 years of follow-up | Number of participants who died from invasive cancer of any type, excluding first 2 years of follow-up |
| Number of Participants With Percutaneous Coronary Intervention | 5 years | Number of participants with percutaneous coronary intervention |
| Number of Participants With Total Coronary Heart Disease | 5 years | Total coronary heart disease = a composite of myocardial infarction, coronary revascularization (percutaneous coronary intervention or coronary-artery bypass grafting), and death from coronary heart disease |
| Number of Participants With Ischemic Stroke | 5 years | Number of participants with ischemic stroke |
| Number of Participants With Hemorrhagic Stroke | 5 years | Number of participants with hemorrhagic stroke |
| Number of Participants Who Died From Myocardial Infarction | 5 years | Number of participants who died from myocardial infarction |
| Number of Participants Who Died From Coronary Heart Disease | 5 years | Number of participants who died from coronary heart disease |
| Number of Participants Who Died From Stroke | 5 years | Number of participants who died from stroke |
| Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up | 5 years, excluding first 2 years of follow-up | Number of participants with myocardial infarction, excluding first 2 years of follow-up |
| Number of Participants With Conventional Colorectal Adenoma | 5 years | tubular, tubulovillous, villous adenoma; adenoma w/high-grade dysplasia |
| Number of Participants With Serrated Colorectal Polyps | 5 years | hyperplastic polyp, traditional serrated adenoma, sessile serrated polyp |
Countries
United States
Participant flow
Recruitment details
401605 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 | PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids | Total | ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids | ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids | PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4007 Participants | 16023 Participants | 4005 Participants | 4002 Participants | 4009 Participants |
| Age, Categorical Between 18 and 65 years | 2467 Participants | 9848 Participants | 2458 Participants | 2462 Participants | 2461 Participants |
| Age, Continuous | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7.1 | 67.1 years STANDARD_DEVIATION 7 | 67.2 years STANDARD_DEVIATION 7.1 |
| Race/Ethnicity, Customized African American | 1282 Participants | 5106 Participants | 1278 Participants | 1275 Participants | 1271 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 102 Participants | 388 Participants | 102 Participants | 86 Participants | 98 Participants |
| Race/Ethnicity, Customized Hispanic (not African American) | 252 Participants | 1013 Participants | 246 Participants | 270 Participants | 245 Participants |
| Race/Ethnicity, Customized Native American/Alaskan Native | 52 Participants | 228 Participants | 62 Participants | 56 Participants | 58 Participants |
| Race/Ethnicity, Customized Non-Hispanic white | 4504 Participants | 18046 Participants | 4515 Participants | 4498 Participants | 4529 Participants |
| Race/Ethnicity, Customized Other/unknown | 141 Participants | 523 Participants | 126 Participants | 133 Participants | 123 Participants |
| Region of Enrollment United States | 6474 Participants | 25871 Participants | 6463 Participants | 6464 Participants | 6470 Participants |
| Sex: Female, Male Female | 3267 Participants | 13085 Participants | 3276 Participants | 3271 Participants | 3271 Participants |
| Sex: Female, Male Male | 3207 Participants | 12786 Participants | 3187 Participants | 3193 Participants | 3199 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 485 / 12,927 | 493 / 12,944 | 493 / 12,933 | 485 / 12,938 | 241 / 6,463 | 244 / 6,464 | 252 / 6,470 | 241 / 6,474 |
| other Total, other adverse events | 10,086 / 12,927 | 10,098 / 12,944 | 10,094 / 12,933 | 10,090 / 12,938 | 5,101 / 6,463 | 5,027 / 6,464 | 5,037 / 6,470 | 5,101 / 6,474 |
| serious Total, serious adverse events | 1,673 / 12,927 | 1,659 / 12,944 | 1,613 / 12,933 | 1,619 / 12,938 | 791 / 6,463 | 782 / 6,464 | 822 / 6,470 | 837 / 6,474 |
Outcome results
Primary
Number of Participants With a Major Cardiovascular Event
Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With a Major Cardiovascular Event | 396 Participants |
| Vitamin D placebo | Number of Participants With a Major Cardiovascular Event | 409 Participants |
| Active omega-3 fatty acids | Number of Participants With a Major Cardiovascular Event | 386 Participants |
| Omega-3 fatty acids placebo | Number of Participants With a Major Cardiovascular Event | 419 Participants |
p-value: 0.6995% CI: [0.85, 1.12]Regression, Cox
p-value: 0.2495% CI: [0.8, 1.06]Regression, Cox
Primary
Number of Participants With Invasive Cancer of Any Type
Number of participants with invasive cancer of any type
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Invasive Cancer of Any Type | 793 Participants |
| Vitamin D placebo | Number of Participants With Invasive Cancer of Any Type | 824 Participants |
| Active omega-3 fatty acids | Number of Participants With Invasive Cancer of Any Type | 820 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Invasive Cancer of Any Type | 797 Participants |
p-value: 0.4795% CI: [0.88, 1.06]Regression, Cox
p-value: 0.5695% CI: [0.93, 1.13]Regression, Cox
Secondary
Number of Female Participants With Breast Cancer
Number of female participants with breast cancer
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Female Participants With Breast Cancer | 124 Participants |
| Vitamin D placebo | Number of Female Participants With Breast Cancer | 122 Participants |
| Active omega-3 fatty acids | Number of Female Participants With Breast Cancer | 117 Participants |
| Omega-3 fatty acids placebo | Number of Female Participants With Breast Cancer | 129 Participants |
p-value: 0.995% CI: [0.79, 1.31]Regression, Cox
p-value: 0.4395% CI: [0.7, 1.16]Regression, Cox
Secondary
Number of Male Participants With Prostate Cancer
Number of male participants with prostate cancer
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Male Participants With Prostate Cancer | 192 Participants |
| Vitamin D placebo | Number of Male Participants With Prostate Cancer | 219 Participants |
| Active omega-3 fatty acids | Number of Male Participants With Prostate Cancer | 219 Participants |
| Omega-3 fatty acids placebo | Number of Male Participants With Prostate Cancer | 192 Participants |
p-value: 0.1995% CI: [0.72, 1.07]Regression, Cox
p-value: 0.1795% CI: [0.94, 1.39]Regression, Cox
Secondary
Number of Participants Who Died From Any Cause
Number of participants who died from any cause
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Any Cause | 485 Participants |
| Vitamin D placebo | Number of Participants Who Died From Any Cause | 493 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Any Cause | 493 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Any Cause | 485 Participants |
p-value: 0.8795% CI: [0.87, 1.12]Regression, Cox
p-value: 0.7995% CI: [0.9, 1.15]Regression, Cox
Secondary
Number of Participants Who Died From Cardiovascular Causes
Number of participants who died from cardiovascular causes
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Cardiovascular Causes | 152 Participants |
| Vitamin D placebo | Number of Participants Who Died From Cardiovascular Causes | 138 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Cardiovascular Causes | 142 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Cardiovascular Causes | 148 Participants |
p-value: 0.3895% CI: [0.88, 1.4]Regression, Cox
p-value: 0.7395% CI: [0.76, 1.21]Regression, Cox
Secondary
Number of Participants Who Died From Invasive Cancer of Any Type
Number of participants who died from invasive cancer of any type
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Invasive Cancer of Any Type | 154 Participants |
| Vitamin D placebo | Number of Participants Who Died From Invasive Cancer of Any Type | 187 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Invasive Cancer of Any Type | 168 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Invasive Cancer of Any Type | 173 Participants |
p-value: 0.0895% CI: [0.67, 1.02]Regression, Cox
p-value: 0.7995% CI: [0.79, 1.2]Regression, Cox
Secondary
Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up
Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes; excluding first 2 years of follow-up
Time frame: 5 years, excluding first 2 years of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up | 274 Participants |
| Vitamin D placebo | Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up | 296 Participants |
| Active omega-3 fatty acids | Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up | 269 Participants |
| Omega-3 fatty acids placebo | Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up | 301 Participants |
p-value: 0.3895% CI: [0.79, 1.09]Regression, Cox
p-value: 0.1895% CI: [0.76, 1.05]Regression, Cox
Secondary
Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint
Expanded composite cardiovascular endpoint = a composite endpoint of myocardial infarction, stroke, death from cardiovascular causes, and coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention)
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint | 536 Participants |
| Vitamin D placebo | Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint | 558 Participants |
| Active omega-3 fatty acids | Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint | 527 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint | 567 Participants |
p-value: 0.5395% CI: [0.86, 1.08]Regression, Cox
p-value: 0.2195% CI: [0.82, 1.04]Regression, Cox
Secondary
Number of Participants With Colorectal Cancer
Number of participants with colorectal cancer
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Colorectal Cancer | 51 Participants |
| Vitamin D placebo | Number of Participants With Colorectal Cancer | 47 Participants |
| Active omega-3 fatty acids | Number of Participants With Colorectal Cancer | 54 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Colorectal Cancer | 44 Participants |
p-value: 0.6795% CI: [0.73, 1.62]Regression, Cox
p-value: 0.3195% CI: [0.83, 1.83]Regression, Cox
Secondary
Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up
Number of participants with invasive cancer of any type, excluding first 2 years of follow-up
Time frame: 5 years, excluding first 2 years of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 490 Participants |
| Vitamin D placebo | Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 522 Participants |
| Active omega-3 fatty acids | Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 536 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 476 Participants |
p-value: 0.3395% CI: [0.83, 1.06]Regression, Cox
p-value: 0.05695% CI: [1, 1.28]Regression, Cox
Secondary
Number of Participants With Myocardial Infarction
Number of participants with myocardial infarction
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Myocardial Infarction | 169 Participants |
| Vitamin D placebo | Number of Participants With Myocardial Infarction | 176 Participants |
| Active omega-3 fatty acids | Number of Participants With Myocardial Infarction | 145 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Myocardial Infarction | 200 Participants |
p-value: 0.7395% CI: [0.78, 1.19]Regression, Cox
p-value: 0.00395% CI: [0.59, 0.9]Regression, Cox
Secondary
Number of Participants With Stroke
Number of participants with stroke
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Stroke | 141 Participants |
| Vitamin D placebo | Number of Participants With Stroke | 149 Participants |
| Active omega-3 fatty acids | Number of Participants With Stroke | 148 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Stroke | 142 Participants |
p-value: 0.6895% CI: [0.76, 1.2]Regression, Cox
p-value: 0.7295% CI: [0.83, 1.31]Regression, Cox
Other Pre-specified
Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up
Number of participants who died from any cause, excluding first 2 years of follow-up
Time frame: 5 years, excluding first 2 years of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up | 368 Participants |
| Vitamin D placebo | Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up | 384 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up | 371 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Any Cause, Excluding First 2 Years of Follow-up | 381 Participants |
p-value: 0.6295% CI: [0.84, 1.11]Regression, Cox
p-value: 0.7295% CI: [0.84, 1.12]Regression, Cox
Other Pre-specified
Number of Participants Who Died From Coronary Heart Disease
Number of participants who died from coronary heart disease
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Coronary Heart Disease | 48 Participants |
| Vitamin D placebo | Number of Participants Who Died From Coronary Heart Disease | 38 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Coronary Heart Disease | 37 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Coronary Heart Disease | 49 Participants |
p-value: 0.2795% CI: [0.83, 1.95]Regression, Cox
p-value: 0.19895% CI: [0.49, 1.16]Regression, Cox
Other Pre-specified
Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up
Number of participants who died from invasive cancer of any type, excluding first 2 years of follow-up
Time frame: 5 years, excluding first 2 years of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 112 Participants |
| Vitamin D placebo | Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 149 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 126 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up | 135 Participants |
p-value: 0.02495% CI: [0.59, 0.96]Regression, Cox
p-value: 0.5895% CI: [0.73, 1.19]Regression, Cox
Other Pre-specified
Number of Participants Who Died From Myocardial Infarction
Number of participants who died from myocardial infarction
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Myocardial Infarction | 24 Participants |
| Vitamin D placebo | Number of Participants Who Died From Myocardial Infarction | 15 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Myocardial Infarction | 13 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Myocardial Infarction | 26 Participants |
p-value: 0.1595% CI: [0.84, 3.06]Regression, Cox
p-value: 0.0495% CI: [0.26, 0.97]Regression, Cox
Other Pre-specified
Number of Participants Who Died From Stroke
Number of participants who died from stroke
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants Who Died From Stroke | 19 Participants |
| Vitamin D placebo | Number of Participants Who Died From Stroke | 23 Participants |
| Active omega-3 fatty acids | Number of Participants Who Died From Stroke | 22 Participants |
| Omega-3 fatty acids placebo | Number of Participants Who Died From Stroke | 20 Participants |
p-value: 0.5895% CI: [0.46, 1.54]Regression, Cox
p-value: 0.7695% CI: [0.6, 2.01]Regression, Cox
Other Pre-specified
Number of Participants With Conventional Colorectal Adenoma
tubular, tubulovillous, villous adenoma; adenoma w/high-grade dysplasia
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Conventional Colorectal Adenoma | 308 Participants |
| Vitamin D placebo | Number of Participants With Conventional Colorectal Adenoma | 287 Participants |
| Active omega-3 fatty acids | Number of Participants With Conventional Colorectal Adenoma | 294 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Conventional Colorectal Adenoma | 301 Participants |
95% CI: [0.92, 1.27]
95% CI: [0.83, 1.15]
Other Pre-specified
Number of Participants With Coronary-artery Bypass Grafting
Number of participants with coronary-artery bypass grafting
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Coronary-artery Bypass Grafting | 73 Participants |
| Vitamin D placebo | Number of Participants With Coronary-artery Bypass Grafting | 98 Participants |
| Active omega-3 fatty acids | Number of Participants With Coronary-artery Bypass Grafting | 85 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Coronary-artery Bypass Grafting | 86 Participants |
p-value: 0.05895% CI: [0.55, 1.01]Regression, Cox
p-value: 0.9495% CI: [0.73, 1.33]Regression, Cox
Other Pre-specified
Number of Participants With Hemorrhagic Stroke
Number of participants with hemorrhagic stroke
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Hemorrhagic Stroke | 19 Participants |
| Vitamin D placebo | Number of Participants With Hemorrhagic Stroke | 25 Participants |
| Active omega-3 fatty acids | Number of Participants With Hemorrhagic Stroke | 25 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Hemorrhagic Stroke | 19 Participants |
p-value: 0.3795% CI: [0.42, 1.38]Regression, Cox
p-value: 0.3795% CI: [0.72, 2.39]Regression, Cox
Other Pre-specified
Number of Participants With Ischemic Stroke
Number of participants with ischemic stroke
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Ischemic Stroke | 117 Participants |
| Vitamin D placebo | Number of Participants With Ischemic Stroke | 110 Participants |
| Active omega-3 fatty acids | Number of Participants With Ischemic Stroke | 111 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Ischemic Stroke | 116 Participants |
p-value: 0.6195% CI: [0.83, 1.39]Regression, Cox
p-value: 0.7495% CI: [0.74, 1.24]Regression, Cox
Other Pre-specified
Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up
Number of participants with myocardial infarction, excluding first 2 years of follow-up
Time frame: 5 years, excluding first 2 years of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up | 108 Participants |
| Vitamin D placebo | Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up | 117 Participants |
| Active omega-3 fatty acids | Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up | 94 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Myocardial Infarction, Excluding First 2 Years of Follow-up | 131 Participants |
p-value: 0.5695% CI: [0.71, 1.2]Regression, Cox
p-value: 0.01495% CI: [0.55, 0.93]Regression, Cox
Other Pre-specified
Number of Participants With Percutaneous Coronary Intervention
Number of participants with percutaneous coronary intervention
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Percutaneous Coronary Intervention | 182 Participants |
| Vitamin D placebo | Number of Participants With Percutaneous Coronary Intervention | 188 Participants |
| Active omega-3 fatty acids | Number of Participants With Percutaneous Coronary Intervention | 162 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Percutaneous Coronary Intervention | 208 Participants |
p-value: 0.7895% CI: [0.79, 1.19]Regression, Cox
p-value: 0.01695% CI: [0.63, 0.95]Regression, Cox
Other Pre-specified
Number of Participants With Serrated Colorectal Polyps
hyperplastic polyp, traditional serrated adenoma, sessile serrated polyp
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Serrated Colorectal Polyps | 172 Participants |
| Vitamin D placebo | Number of Participants With Serrated Colorectal Polyps | 169 Participants |
| Active omega-3 fatty acids | Number of Participants With Serrated Colorectal Polyps | 174 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Serrated Colorectal Polyps | 167 Participants |
95% CI: [0.82, 1.26]
95% CI: [0.84, 1.29]
Other Pre-specified
Number of Participants With Total Coronary Heart Disease
Total coronary heart disease = a composite of myocardial infarction, coronary revascularization (percutaneous coronary intervention or coronary-artery bypass grafting), and death from coronary heart disease
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active vitamin D | Number of Participants With Total Coronary Heart Disease | 332 Participants |
| Vitamin D placebo | Number of Participants With Total Coronary Heart Disease | 346 Participants |
| Active omega-3 fatty acids | Number of Participants With Total Coronary Heart Disease | 308 Participants |
| Omega-3 fatty acids placebo | Number of Participants With Total Coronary Heart Disease | 370 Participants |
p-value: 0.6195% CI: [0.83, 1.12]Regression, Cox
p-value: 0.01695% CI: [0.71, 0.97]Regression, Cox