To determine whether reduction of cholesterol by drug therapy significantly lowered the atherosclerotic coronary heart disease rate in a group of hypercholesterolemic but otherwise healthy men. Total dollars spent on the CPPT from June 1973 were $142,250,000. We do not have a year-by-year breakdown...
Date First Received: October 27, 1999
Last Updated: June 23, 2005
Verified by: National Heart, Lung, and Blood Institute (NHLBI), June 2000
Clinical Trial Phase: Phase 3 | Start Date: June 1973
Overall Status: Completed
Brief Summary
Condition Keyword(s):
Intervention(s):
To determine whether reduction of cholesterol by drug therapy significantly lowered the atherosclerotic coronary heart disease rate in a group of hypercholesterolemic but otherwise healthy men.
Total dollars spent on the CPPT from June 1973 were $142,250,000. We do not have a year-by-year breakdown.
Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind
Detailed Clinical Trial Description
BACKGROUND:
Numerous prospective epidemiologic studies have demonstrated that hypercholesterolemia is a major risk factor for atherosclerotic coronary heart disease. Research on animals indicating that the reduction of serum cholesterol prevented or reversed atherosclerosis had not been shown convincingly in humans. The Coronary Primary Prevention Trial tested the hypothesis that lowering the serum cholesterol in patients who had no existing evidence of coronary heart disease would reduce the subsequent rate of coronary heart disease in those persons.
Coronary heart disease is the leading cause of death and a major cause of morbidity in the United States. The very slow development of the underlying arterial disease and its frequently sudden onset and quickly fatal course necessitate a preventive approach if substantial inroads are to be made. The positive result from the Coronary Primary Prevention Trial (CPPT) has done much to resolve the controversy regarding the benefits of lipid-lowering, and should lead to firm advice for high-risk hypercholesterolemic subjects and for the population as a whole.
The CPPT was part of the Institute's Lipid Research Clinic Program under the Lipid Metabolism Branch, DHVD, NHLBI. Twelve lipid research clinics in the United States and Canada participated in this trial, as well as a coordinating center, a central electrocardiographic laboratory, central lipid and clinical chemistry laboratories, a nutrition coding center, and a group of consultants on recruitment and adherence. This program's objectives included the development of standardized methods and definitions for the diagnosis of hyperlipoproteinemia and the performance of a series of collaborative studies of the prevalence and natural history of this disorder, as well as the design and implementation of the Coronary Primary Prevention Trial.
The protocol for the trial was approved in November 1972. Beginning in July 1973, men with hypercholesterolemia were recruited as potential trial subjects from such diverse sources as physician referrals, blood bank donor lists, and mass screening programs. Each subject was screened further in a series of four visits, the purpose of which was to select only men (1) whose lipid abnormality was of the primary Type II phenotype, (2) who were free of clinically manifest coronary heart disease, and (3) whose excellent overall health and reliability made 7-10 years of follow-up a realistic objective. Additionally, a standardized limited-cholesterol/saturated fat diet was initiated at the second of these visits in order to exclude men whose cholesterol levels were highly responsive to diet. Subjects who met all the selection criteria were randomly assigned, in a double-blind fashion, to receive either the cholesterol-lowering drug cholestyramine or a placebo at their fifth visit.
Recruitment of the 3,806 CPPT subjects was completed in July 1976. After randomization into the study, each subject visited his clinic at bimonthly intervals. At these visits, adherence to drug and diet were assessed, the study medication was supplied, general health and potential toxic side effects were monitored, and intervening cardiovascular events were recorded. Counseling in drug and dietary adherence were given at each visit, and medical advice was given when a problem was identified. Trial data were collected and analyzed at the Central Patient Registry and reviewed periodically by a Safety and Data Monitoring Board.
Intervention ceased between May and August 1983. A five-year follow-up was initiated in November 1984 to detect possible toxicity in the CPPT participants following ingestion of cholestyramine (or placebo) for 7 to 10 years. Follow-up was completed in October 1989.
DESIGN NARRATIVE:
Randomized, double-blind, fixed sample size with one experimental group and one control group of equal size. Experimental group on diet and lipid-lowering drug regimen; control group on diet and placebo regimen.
Intervention(s) in this Clinical Trial
- Drug: cholestyramine
- Behavioral: diet, fat-restricted
Criteria for Participation in this Clinical Trial
- Men, ages 35-59. Type II hyperlipoproteinemia. Free from coronary heart disease.
Gender Eligibility for this Clinical Trial: Male
Minimum Age for this Clinical Trial: 35 Years
Maximum Age for this Clinical Trial: 59 Years
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Overall Clinical Trial Officials and Contacts
Francois Abboud University of Iowa
Related Publications
References
[No authors listed] The coronary primary prevention trial: design and implementation: the Lipid Research Clinics Program. J Chronic Dis. 1979;32(9-10):609-31. No abstract available.
Agras WS, Marshall G. Recruitment for the Coronary Primary Prevention Trial. Clin Pharmacol Ther. 1979 May;25(5 Pt 2):688-90.
Rifkind B, Goor R: The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). Drugs Affecting Lipid Metabolism, l5l-l57, Fumagalli R, Kritchevsky D, Paoletti R (Eds): Elsevier/North-Holland Biomedical Press, l980.
Knopp RH: Test of the Lipid Hypothesis: The Coronary Primary Prevention Trial (CPPT) of the Lipid Research Clinics Program. Proceedings of the Fifth International Symposium on Atherosclerosis, 509-512, Gotto, AM, Jr. (Ed.): Springer-Verlag, 1980.
[No authors listed] Recruitment for clinical trials: the Lipid Research Clinics Coronary Primary Prevention Trial experience. Its implications for future trials. Circulation. 1982 Dec;66(6 Pt 2):IV1-78. No abstract available.
Gordon DJ, Salz KM, Roggenkamp KJ, Franklin FA Jr. Dietary determinants of plasma cholesterol change in the recruitment phase of the Lipid Research Clinics Coronary Primary Prevention Trial. Arteriosclerosis. 1982 Nov-Dec;2(6):537-48.
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[No authors listed] Participant recruitment to the Coronary Primary Prevention Trial. J Chronic Dis. 1983;36(6):451-65.
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[No authors listed] The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984 Jan 20;251(3):351-64.
[No authors listed] The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984 Jan 20;251(3):365-74.
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[No authors listed] NHLBI workshop on the Lipid Research Clinics Coronary Primary Prevention Trial. Arteriosclerosis. 1985 Jul-Aug;5(4):397-403. No abstract available.
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[No authors listed] The Lipid Research Clinics Coronary Primary Prevention Trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators. Arch Intern Med. 1992 Jul;152(7):1399-410.
Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Ordovas JM, Davis CE, Abolafia JM, Lippel K, Levy RI. Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial. JAMA. 1994 Apr 6;271(13):999-1003.
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Additional Information
Information obtained from ClinicalTrials.gov on August 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000488
Study ID Number: 7
ClinicalTrials.gov Identifier: NCT00000488
Health Authority: United States: Federal Government
Clinical Trials Authorship and Review
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
