Cholesterol-Lowering Atherosclerosis Study (CLAS)
Condition: Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis
MeSH terms: Cerebrovascular Disorders; Carotid Artery Diseases; Intracranial Arteriosclerosis; Cardiovascular Diseases; Atherosclerosis; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine whether combined therapy with the lipid lowering agents colestipol hydrochloride
      plus niacin would produce significant change in coronary, carotid, and femoral artery
      atherosclerosis and coronary bypass graft lesions as determined by angiography. Also, to
      determine possible correlations between lesion changes and plasma lipid and lipoprotein
      cholesterol levels and to explore interrelationships of atherosclerosis change in femoral,
      coronary, and carotid arteries.
    

Detailed description: 
      BACKGROUND:

      The Lipid Research Clinics Coronary Primary Prevention Trial and the Coronary Drug Project
      had shown that morbidity and mortality from ischemic heart disease were reduced by blood
      cholesterol-lowering therapy. Although blood cholesterol reduction ameliorated experimental
      atherosclerosis in animal models, the two largest human studies with angiographic observation
      of arterial lesion change, the NHLBI Type II Coronary Intervention Study and a study by Cohn
      et al, had not demonstrated significant treatment effects. Favorable, but inconclusive,
      treatment trends were observed in four unrandomized angiographic trials and one trial too
      small for evaluation of randomized groups.

      The clinical trial was supported by a subproject within a program project grant.

      DESIGN NARRATIVE:

      CLAS-I was randomized and selectively-blinded. Screening for the trial consisted of five
      clinic visits, at which baseline data, including angiographic data, were obtained and a
      prerandomization trial of the study drugs was conducted. One hundred eighty-eighty subjects
      were randomized to either 30 grams (g) of colestipol hydrochloride plus 3 to 12 g of niacin
      daily or to placebo. Both groups received diet intervention. The drug group received less
      than 125 milligrams (mg) of cholesterol daily, 22 percent of energy as fat, 10 percent as
      polyunsaturated fat, and 4 percent as saturated fat. The placebo group received less than 250
      mg of cholesterol per day, 26 percent of energy as fat, 10 percent as polyunsaturated fat,
      and 5 percent as saturated fat. The different diet composition for drug and placebo groups
      was to enhance the differential in blood cholesterol responses between the two groups. Study
      subjects and clinic staff were blinded to the prerandomization study drug trial lipid
      responses. Subjects were blinded to treatment assignments. Subjects and staff were not
      blinded to on-trial lipid values. The primary endpoint, the global change score, was change
      in atherosclerosis observed by angiography of native coronary arteries and aorta coronary
      bypass grafts. Evaluation of study end-points was performed by staff and consultants who were
      blinded to treatment group assignments, as well as to the temporal ordering of angiographic
      data. Subjects were seen monthly for the first six months and then at two-month intervals. A
      repeat angiogram was performed at two years. Of the 188 randomized subjects, 162 completed
      the study.

      On completion of CLAS-I, participants not requiring further bypass surgery were invited to
      continue in CLAS-II for an additional two years on their previously assigned treatment.
      Blinded study methods were maintained; there was no crossover between treatments. One hundred
      thirty-eight subjects continued in CLAS-II; 103 completed a third angiogram before the CLAS-I
      outcome was known and CLAS-II terminated. The CLAS-II clinical procedures, lipid,
      lipoprotein-cholesterol, and apolipoprotein analyses were the same as in CLAS-I. The CLAS-II
      angiographic and file evaluation procedures exactly replicated those in CLAS-I.

      The study completion date listed in this record was obtained from the Query/View/Report (QVR)
      System.
    

Intervention name(s): colestipol; niacin; diet, fat-restricted
Intervention type(s): Drug; Drug; Behavioral
Intervention MeSH terms: Niacin; Colestipol
Allocation: Randomized
Primary purpose: Treatment