Trial record 6 of 366 for:    Cerebral Arteriosclerosis

Asymptomatic Carotid Artery Plaque Study (ACAPS)

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00000469
First received: October 27, 1999
Last updated: June 23, 2005
Last verified: April 2000
  Purpose

To determine whether warfarin or lovastatin alone or in combination retarded the progression of atherosclerotic plaques in the carotid arteries of high risk individuals with asymptomatic carotid stenosis. Also, to determine if a full scale trial was feasible.


Condition Intervention Phase
Cardiovascular Diseases
Carotid Stenosis
Cerebral Arteriosclerosis
Cerebrovascular Disorders
Heart Diseases
Vascular Diseases
Drug: aspirin
Drug: lovastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: May 1988
Estimated Study Completion Date: August 1998
Detailed Description:

BACKGROUND:

At the present time, atherosclerosis of the major extracranial arteries to the brain is considered the cause of most strokes. Early intervention and stroke prevention utilized anti-coagulants such as coumadin and heparin. Results were largely equivocal due to the diverse nature of the underlying pathogenesis and due to problems that offset potential benefit. Emphasis gradually switched to aspirin and to other platelet anti-aggregant drugs because of mounting evidence that micro-emboli were a major element in transient ischemic attacks. Several studies have examined the potential benefit of aspirin in stroke prevention. The exact dose of aspirin that was maximally beneficial with minimal side effects was not completely established. There was evidence that low dose aspirin was as effective as higher doses. The American College of Chest Physicians (ACCP) made recommendations that if aspirin were issued as a primary anti-thrombotic agent, the dose should be 325 mg daily, except in patients with cerebrovascular disease in whom the lowest beneficial dose appeared to be one gram per day. The ACCP also pointed out that the risk of bleeding was substantially greater in patients with ischemic cerebrovascular disease and venous thromboembolism than in other high risk groups requiring anticoagulation. It advised that anticoagulant therapy was not needed, but that aspirin might be given at 325 mg per day.

Lovastatin is a fungal metabolite that inhibits 3-hydroxy, 3-methyl glutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol biosynthesis in human cells including the liver. Inhibition of this pathway causes the cells to increase their low density lipoprotein receptor numbers to compensate, causing a reduction in circulating low density lipoprotein levels with a consequent drop in circulating plasma cholesterol levels. The drug also raises high density lipoprotein levels significantly. A favorable outcome of the trial will have major public health implications for the prevention and control of atherosclerosis and its complications.

DESIGN NARRATIVE:

Randomized, double-blind, factorial design. In this multicenter study, patients were assigned to one of four drug combination groups: active lovastatin/active warfarin, active lovastatin/warfarin placebo, lovastatin placebo/active warfarin, and lovastatin placebo/warfarin placebo. Daily aspirin was recommended for everyone. Ultrasound was performed for screening, at baseline and semiannually thereafter. Lipid profiles were obtained at screening, at baseline, monthly for the first three months, at six months, and annually thereafter, with beta quantification at baseline. Recruitment began in the tenth month of the trial and continued for one year, ending in September 1990. Treatment continued through the 51st month. Average treatment period was 2.7 years. Subjects were offered a dietary regimen for three months prior to receiving any drug therapy. Only those individuals whose lipid levels did not fall below a certain point continued in dietary intervention. The primary outcome measure was the three year change in mean maximum intimal-medial thickness (IMT) in twelve walls of the carotid arteries. Secondary outcomes included change in single maximum IMT and incidence of major cardiovascular events.

In 1995, an R03 was awarded to Mark Espeland to extend analyses of the carotid B-mode ultrasound data through August, 1998.

  Eligibility

Ages Eligible for Study:   40 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Men and women with early carotid atherosclerosis and moderately elevated LDL cholesterol between the 60th and 90th percentiles.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000469

Sponsors and Collaborators
Investigators
Investigator: Mark Espeland Bowman Gray School of Medicine
Investigator: Curt Furberg Bowman Gray School of Medicine
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00000469     History of Changes
Other Study ID Numbers: 58
Study First Received: October 27, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Intracranial Arteriosclerosis
Brain Diseases
Vascular Diseases
Cardiovascular Diseases
Heart Diseases
Carotid Stenosis
Cerebrovascular Disorders
Arterial Occlusive Diseases
Carotid Artery Diseases
Central Nervous System Diseases
Nervous System Diseases
Intracranial Arterial Diseases

ClinicalTrials.gov processed this record on September 16, 2014