Clinical trial NCT00116870: MARS - Monitored Atherosclerosis Regression Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Atherosclerosis
Coronary Artery Disease
Keywords: CAD
familial hypercholesterolemia
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
First posted: 2005-07-01
Enrollment: 270
Sex: ALL
Minimum age (years): 21
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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 outcomes:
measure: average (per-patient) change in minimum lumen diameter assessed by quantitative angiography
measure: the global change score assessed by a human panel
measure: the proportion of patients with progression or regression of disease assessed by quantitative coronary angiography
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine
state: California
Study officials:
affiliation: University of Southern California, Atherosclerosis Research Unit, Division of Cardiovascular Medicine, Department of Medicine
name: Howard N. Hodis, MD
role: PRINCIPAL_INVESTIGATOR
References: