The VA HDL Intervention Trial (HIT): Secondary Prevention of Coronary Heart Disease in Men With Low HDL-Cholesterol and Desirable LDL-Cholesterol (HIT)

October 20, 2015 updated by: VA Office of Research and Development

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

2531

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Health Care System, Minneapolis, MN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 73 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

Inclusion criteria:

  1. male gender
  2. age 73 or younger
  3. presence of CHD
  4. HDL-C le 40 mg/dl
  5. LDL-C le 140 mg/dl
  6. triglycerides le 300 mg/dl

Exclusion Criteria:

Exclusion criteria:

  1. significant medical illness
  2. alcohol or substance abuse
  3. evidence of cholecystitis or cholelithiasis
  4. ejection fraction of lt 35%
  5. current use of steroids, estrogens, immunosuppressive agents, oral coagulants, or lipid modifying drug.
  6. allergic to gemfibrozil or fibric acid
  7. refused informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Gemfibrozil
1200 mg slow-release gemfibrozil (Lopid-SR) once per day
Drug: gemfibrozil
Placebo Comparator: Placebo
Matching placebo tablets taken once per day
Other: Placebo
Matching placebo tablets taken once per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
incidence of nonfatal myocardial infarction or death from coronary heart disease
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Collaborators

Parke-Davis
Fournier Labs

Investigators

  • Study Chair: Hanna E. Bloomfield, MD MPH, Minneapolis VA Health Care System, Minneapolis, MN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1991

Primary Completion (Actual)

September 1, 1998

Study Completion (Actual)

August 1, 1999

Study Registration Dates

First Submitted

January 25, 2006

First Submitted That Met QC Criteria

January 26, 2006

First Posted (Estimate)

January 27, 2006

Study Record Updates

Last Update Posted (Estimate)

October 21, 2015

Last Update Submitted That Met QC Criteria

October 20, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 363

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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