Coronary Heart DiseasePhase 3HITNCT00283335
The VA HDL Intervention Trial (HIT): Secondary Prevention of Coronary Heart Disease in Men With Low HDL-Cholesterol and Desirable LDL-Cholesterol
A Phase 3 study testing gemfibrozil in people with Coronary Heart Disease, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This was a double-blind randomized trial comparing 1200 mg per day of gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL-C of 40mg/dl or less, an LDL-C of 140 mg/dl or less, and triglycerides of 300mg/dl or less. Read more about this study
- Who is it for?
- Ages Up to 73 years, men only
- Conditions the study is for
- Coronary Heart Disease
- What is being tested?
- gemfibrozil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,531 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1991to Aug 1999
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 73 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- male gender
- age 73 or younger
- presence of CHD
- HDL-C le 40 mg/dl
- LDL-C le 140 mg/dl
- triglycerides le 300 mg/dl
Who cannot join
- significant medical illness
- alcohol or substance abuse
- evidence of cholecystitis or cholelithiasis
- ejection fraction of lt 35%
- current use of steroids, estrogens, immunosuppressive agents, oral coagulants, or lipid modifying drug.
- allergic to gemfibrozil or fibric acid
- refused informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417
About this study
Official title: CSP #363 - The VA HDL Intervention Trial (HIT): Secondary Prevention of Coronary Heart Disease in Men With Low HDL-Cholesterol and Desirable LDL-Cholesterol
This was a double-blind randomized trial comparing 1200 mg per day of gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL-C of 40mg/dl or less, an LDL-C of 140 mg/dl or less, and triglycerides of 300mg/dl or less. The primary outcome was nonfatal myocardial infarction(MI) or death from coronary causes. The median follow-up was 5.1 years. There was a risk reduction of 22% in the primary outcome (p=.0006) and 24% risk reduction in the combined endpoint of stroke, MI, and CHD death. The rate of events was reduced by raising HDL-C and lowering triglycerides without lowering LDL-C (N Engl J Med 1999;341:410-418).
Read the detailed description
Primary Hypothesis:
To determine if drug treatment aimed at raising HDL-cholesterol and lowering triglycerides will reduce the rate of heart attack and death in veterans with coronary heart disease (CHD) and a specific lipid profile characterized by normal levels of LDL-cholesterol and low levels of HDL-cholesterol.
Secondary Hypotheses:
To determine the effect of treatment on total mortality, unstable angina, CABG, PTCA, strokes and PVD, and to determine whether there is an association between changes in plasma lipid levels and outcomes.
Primary Outcomes:
Myocardial infarction (MI), silent MI, and CHD death.
Interventions:
Gemfibrozil (1200 mg per day) versus matching placebo.
Study Abstract:
A double-blind trial was conducted comparing gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg/dL or less, and an LDL cholesterol level of 140 mg/dL or less.
The median follow-up was 5.1 years. At one year, the mean HDL was 6% higher, the mean triglyceride were 31% lower, and the mean total cholesterol was 4% lower in the gemfibrozil group than in the placebo group. LDL levels did not differ between the groups.
A primary event (MI or death) occurred in 275 of the 1267 placebo patients (21.7%) and in 219 of the 1264 gemfibrozil patients (17.3%). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22% (95% confidence interval, 7% to 35%; p=0.006). A 24% relative risk reduction occurred in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (p<0.001). Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.
The major findings were published in the New England Journal of Medicine in August, 1999. A paper on lipid screening was published in the Journal of Clinical Epidemiology in July, 1999 and one on clinical implications was published in the European Heart Journal. Our cost analysis shows that gemfibrozil therapy is highly cost-effective if not cost-saving, thus providing a strong rationale for incorporating results into clinical practice. A manuscript about lipids as predictors of endpoints was published in JAMA in March, 2001. Another paper on stroke was published in Circulation in June, 2001. Dr. Robins presented data on diabetics in November, 2000 at the AHA. A paper on cost-effectiveness was published in the Archives of Internal Medicine in January 2002. A manuscript on diabetes has been accepted by the Archives of Internal Medicine.
A NHLBI grant for continuing analysis has been funded for two years. Other papers in progress include homocysteines in diabetics, fasting plasma insulin as a predictor of outcome, and the effect of lipoprotein subclass particle size on coronary events.
- Conditions
- Coronary Heart Disease
- Being tested
- gemfibrozil, Placebo
- Medical subject headings
- Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemfibrozilDrug
PlaceboOther
Matching placebo tablets taken once per day
| Study group | Role | What they receive |
|---|---|---|
| Gemfibrozil | Active comparator | 1200 mg slow-release gemfibrozil (Lopid-SR) once per day Receives: Drug: gemfibrozil |
| Placebo | Placebo comparator | Matching placebo tablets taken once per day Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of nonfatal myocardial infarction or death from coronary heart disease
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startJun 1991
- Primary completionSep 1998
- Study completionAug 1999
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Coronary Heart DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,531 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Parke-Davis, Fournier Labs
- Responsible party
- Sponsor
- Investigators
- Hanna E. Bloomfield, MD MPH, Study chair, Minneapolis VA Health Care System, Minneapolis, MN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00283335
- Sponsor's protocol ID
- 363
- Acronym
- HIT
- Status last verified
- Oct 2015
- First submitted
- 25 Jan 2006
- Last updated
- 21 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brousseau ME, O'Connor JJ Jr, Ordovas JM, Collins D, Otvos JD, Massov T, McNamara JR, Rubins HB, Robins SJ, Schaefer EJ. Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1148-54. doi: 10.1161/01.atv.0000024566.57589.2e.
PubMed 12117730Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410-8. doi: 10.1056/NEJM199908053410604.
PubMed 10438259Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, Faas FH, Anderson JW. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med. 2002 Dec 9-23;162(22):2597-604. doi: 10.1001/archinte.162.22.2597.
PubMed 12456232Papademetriou V, Narayan P, Rubins H, Collins D, Robins S. Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels. HIT Investigators. Department of Veterans Affairs HDL Intervention Trial. Am Heart J. 1998 Oct;136(4 Pt 1):734-40. doi: 10.1016/s0002-8703(98)70023-7.
PubMed 9778079Rubins HB, Robins SJ, Collins D. The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group. Am J Cardiol. 1996 Sep 1;78(5):572-5. doi: 10.1016/s0002-9149(96)00369-4.
PubMed 8806347
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CSP #363 - The VA HDL Intervention Trial (HIT): Secondary Prevention of Coronary Heart Disease in Men With Low HDL-Cholesterol and Desirable LDL-Cholesterol
- ClinicalTrials.gov ID
- NCT00283335
- Acronym / sponsor ID
- HIT / 363
- Conditions
- Coronary Heart Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,531 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Parke-Davis, Fournier Labs
- Study start
- Jun 1991
- Primary completion
- Sep 1998 (actual)
- Study completion
- Aug 1999 (actual)
- First posted
- 27 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a double-blind randomized trial comparing 1200 mg per day of gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL-C of 40mg/dl or less, an LDL-C of 140 mg/dl or less, and triglycerides of 300mg/dl or less. The primary outcome was nonfatal myocardial infarction(MI) or death from coronary causes. The median follow-up was 5.1 years. There was a risk reduction of 22% in the primary outcome (p=.0006) and 24% risk reduction in the combined endpoint of stroke, MI, and CHD death. The rate of events was reduced by raising HDL-C and lowering triglycerides without lowering LDL-C (N Engl J Med 1999;341:410-418).
Detailed description
Primary Hypothesis:
To determine if drug treatment aimed at raising HDL-cholesterol and lowering triglycerides will reduce the rate of heart attack and death in veterans with coronary heart disease (CHD) and a specific lipid profile characterized by normal levels of LDL-cholesterol and low levels of HDL-cholesterol.
Secondary Hypotheses:
To determine the effect of treatment on total mortality, unstable angina, CABG, PTCA, strokes and PVD, and to determine whether there is an association between changes in plasma lipid levels and outcomes.
Primary Outcomes:
Myocardial infarction (MI), silent MI, and CHD death.
Interventions:
Gemfibrozil (1200 mg per day) versus matching placebo.
Study Abstract:
A double-blind trial was conducted comparing gemfibrozil with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg/dL or less, and an LDL cholesterol level of 140 mg/dL or less.
The median follow-up was 5.1 years. At one year, the mean HDL was 6% higher, the mean triglyceride were 31% lower, and the mean total cholesterol was 4% lower in the gemfibrozil group than in the placebo group. LDL levels did not differ between the groups.
A primary event (MI or death) occurred in 275 of the 1267 placebo patients (21.7%) and in 219 of the 1264 gemfibrozil patients (17.3%). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22% (95% confidence interval, 7% to 35%; p=0.006). A 24% relative risk reduction occurred in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (p<0.001). Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.
The major findings were published in the New England Journal of Medicine in August, 1999. A paper on lipid screening was published in the Journal of Clinical Epidemiology in July, 1999 and one on clinical implications was published in the European Heart Journal. Our cost analysis shows that gemfibrozil therapy is highly cost-effective if not cost-saving, thus providing a strong rationale for incorporating results into clinical practice. A manuscript about lipids as predictors of endpoints was published in JAMA in March, 2001. Another paper on stroke was published in Circulation in June, 2001. Dr. Robins presented data on diabetics in November, 2000 at the AHA. A paper on cost-effectiveness was published in the Archives of Internal Medicine in January 2002. A manuscript on diabetes has been accepted by the Archives of Internal Medicine.
A NHLBI grant for continuing analysis has been funded for two years. Other papers in progress include homocysteines in diabetics, fasting plasma insulin as a predictor of outcome, and the effect of lipoprotein subclass particle size on coronary events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemfibrozil | Active comparator | Drug: gemfibrozil1200 mg slow-release gemfibrozil (Lopid-SR) once per day |
| Placebo | Placebo comparator | Other: PlaceboMatching placebo tablets taken once per day |
Who may qualify
- Ages
- Up to 73 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- male gender
- age 73 or younger
- presence of CHD
- HDL-C le 40 mg/dl
- LDL-C le 140 mg/dl
Key exclusion criteria (7 listed)
- significant medical illness
- alcohol or substance abuse
- evidence of cholecystitis or cholelithiasis
- ejection fraction of lt 35%
- current use of steroids, estrogens, immunosuppressive agents, oral coagulants, or lipid modifying drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gemfibrozil | Drug | Gemfibrozil |
| PlaceboMatching placebo tablets taken once per day | Other | Placebo |
Primary outcome
incidence of nonfatal myocardial infarction or death from coronary heart disease
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2015.
- Results publication: PubMed 12117730Brousseau ME, O'Connor JJ Jr, Ordovas JM, Collins D, Otvos JD, Massov T, McNamara JR, Rubins HB, Robins SJ, Schaefer EJ. Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1148-54. doi: 10.1161/01.atv.0000024566.57589.2e.
- Results publication: PubMed 10438259Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410-8. doi: 10.1056/NEJM199908053410604.
- Results publication: PubMed 12456232Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, Faas FH, Anderson JW. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med. 2002 Dec 9-23;162(22):2597-604. doi: 10.1001/archinte.162.22.2597.
- Results publication: PubMed 9778079Papademetriou V, Narayan P, Rubins H, Collins D, Robins S. Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels. HIT Investigators. Department of Veterans Affairs HDL Intervention Trial. Am Heart J. 1998 Oct;136(4 Pt 1):734-40. doi: 10.1016/s0002-8703(98)70023-7.
- Results publication: PubMed 8806347Rubins HB, Robins SJ, Collins D. The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group. Am J Cardiol. 1996 Sep 1;78(5):572-5. doi: 10.1016/s0002-9149(96)00369-4.
Related trials for Coronary Heart Disease
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Active, not recruiting
Shockwave™ vs Surgical Endarterectomy for Calcified Severe Common Femoral Artery Stenosis: Comparison of Efficacy, Safety and Long-Term Outcomes
Common Femoral Artery Stenosis, Calcification; Heart
RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanna E. Bloomfield, MD MPH study chair
Minneapolis VA Health Care System, Minneapolis, MN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing gemfibrozil in people with Coronary Heart Disease, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of nonfatal myocardial infarction or death from coronary heart disease (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00283335, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2015.