MARS - Monitored Atherosclerosis Regression Study

Coronary Artery Disease Clinical Trial

Official title:

A Double-Blind, Placebo-Controlled Angiographic Study to Evaluate the Effect of Lovastatin on the Progression Rate of Atherosclerosis in the Coronary Arteries of Patients With Coronary Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00116870
• Other study ID #: AG0027
• Secondary ID: MK-803
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 30, 2005
• Last updated: December 9, 2009
• Start date: June 1985
• Est. completion date: February 1992

Study information

• Verified date: June 2005
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether significant alterations in serum lipoproteins as provided by the drug lovastatin can substantially reduce atherosclerosis progression or even induce regression.

Description:

Two conceptual advances occurring in the 1980's made it possible to test the hypothesis that significant alterations in serum lipoproteins can substantially reduce atherosclerosis progression or even induce regression. The first advance was in the development of arteriograms used in characterizing atherosclerosis, greatly reducing the number of patients required for the evaluation of an intervention designed to prevent coronary atherosclerosis progression. The second advance was the development of lovastatin that provides a lipid-lowering alternative much easier to tolerate than the niacin/colestipol combination previously used, and has been shown to be comparably effective for LDL reduction in patients with a family history of high cholesterol.

A total of 270 high-risk coronary artery disease patients, not eligible for coronary artery bypass surgery, were recruited for the study. All patients received angiograms and were randomly assigned to either the lovastatin or placebo groups stratified by three baseline factors: sex, smoking status, and plasma cholesterol levels.

Patients initially received lovastatin 40mg twice a day or a matching placebo. Those patients receiving lovastatin whose total plasma cholesterol level was less than 110mg/dL at one visit or 120 mg/dL on two successive visits had their dosage halved, and were maintained on the optimal dosage for the remainder of the study. Coronary angiography was performed prior to screening and at month 24 (visit 18). Angiographic assessment of both femoral arteries was also performed at baseline and at month 24. Noninvasive ultrasound imaging of the carotid arteries (including carotid intima-media thickness) was performed every 6 months. Patients reported to the clinic monthly for 12 months, and at two-month intervals thereafter. Plasma lipids, routine laboratory safety and physical examinations were also performed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: February 1992
• Est. primary completion date: February 1992
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 67 Years

Eligibility

Inclusion Criteria:

• Angiography within 17 weeks of randomization showing patient is at high risk for coronary artery disease but not a candidate for coronary artery graft surgery

• Men and women ages 21 through 67 years

• Mean plasma cholesterol levels from the first two screening visits in the range of 190 to 270 mg/dL

• Smokers are admitted, but encouraged to stop smoking tobacco

Exclusion Criteria:

• Premenopausal women unless surgically sterilized

• Hypertension, diabetes, thyroid disease, liver dysfunction, renal insufficiency, congestive heart failure, major arrhythmia, left ventricular conduction defects

• Physical impairment that may interfere with participation

• Life threatening disease with high likelihood of disability or death during the trial period

• Use of hydralazine, guanethidine, lipid-lowering drugs, estrogens, steroids, amphetamines, antibiotics, theophylline, acetaminophen (average daily use greater than ten grains), other drugs as determined by the principle investigator

• Vitamins A or D in doses greater than the Recommended Daily Allowance (RDA)

• Alcohol abuse

• Nutritional supplements high in cholesterol content

• Chelation therapy

• Psychosocial situations which make completion of the study unlikely

• Hypersensitivity to any component of the study medication

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• lovastatin

Locations

Country	Name	City	State
United States	Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the average (per-patient) change from baseline in percent diameter stenosis in all lesions that showed 20% diameter stenosis at baseline or at follow-up as evaluated by quantitative coronary angiography
Secondary	average (per-patient) change in minimum lumen diameter assessed by quantitative angiography
Secondary	the global change score assessed by a human panel
Secondary	the proportion of patients with progression or regression of disease assessed by quantitative coronary angiography