Lipid Research Clinics Coronary Primary Prevention Trial (CPPT)

NCT ID: NCT00000488

Last Updated: 2016-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 1973-06-30
• Study Completion Date: 1989-10-31

Brief Summary

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.

Detailed 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.

Conditions

Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Interventions

cholestyramine

Intervention Type: DRUG

diet, fat-restricted

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

Men, ages 35-59. Type II hyperlipoproteinemia. Free from coronary heart disease.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Principal Investigators

Francois Abboud

Role:

University of Iowa

Elizabeth Barrett-Connor

Role:

University of California, San Diego

Reagan Bradford

Role:

Oklahoma Medical Research Foundation

Marilyn Buzzard

Role:

University of Minnesota

Gerald Cooper

Role:

Centers for Disease Control and Prevention

John Farquhar

Role:

Stanford University

Ivan Frantz

Role:

University of Minnesota

Anne Goldberg

Role:

Washington University School of Medicine

Frank Ibbott

Role:

Bio-Science Laboratories

William, Insull

Role:

Baylor College of Medicine

Robert Knoop

Role:

University of Washington

Peter Kwiterovich

Role:

Johns Hopkins University

John LaRosa

Role:

George Washington University

J. Little

Role:

University of Toronto

L. Sheffield

Role:

University of Alabama at Birmingham

Dennis Sprecher

Role:

University of Cincinnati

References

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Reference Type: BACKGROUND

PMID: 489702 (View on PubMed)

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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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 7127710 (View on PubMed)

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. doi: 10.1161/01.atv.2.6.537.

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Gordon DJ, Witztum JL, Hunninghake D, Gates S, Glueck CJ. Habitual physical activity and high-density lipoprotein cholesterol in men with primary hypercholesterolemia. The Lipid Research Clinics Coronary Primary Prevention Trial. Circulation. 1983 Mar;67(3):512-20. doi: 10.1161/01.cir.67.3.512.

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Gordon DJ, Probstfield JL, Rubenstein C, Bremner WF, Leon AS, Karon JM, Third J, Bryan H, Schwartz L, Insull W, et al. Coronary risk factors and exercise test performance in asymptomatic hypercholesterolemic men: application of proportional hazards analysis. Am J Epidemiol. 1984 Aug;120(2):210-24. doi: 10.1093/oxfordjournals.aje.a113883.

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 3911061 (View on PubMed)

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Reference Type: BACKGROUND

Gordon DJ, Knoke J, Probstfield JL, Superko R, Tyroler HA. High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial. Circulation. 1986 Dec;74(6):1217-25. doi: 10.1161/01.cir.74.6.1217.

Reference Type: BACKGROUND

PMID: 3536151 (View on PubMed)

Glueck CJ, Gordon DJ, Nelson JJ, Davis CE, Tyroler HA. Dietary and other correlates of changes in total and low density lipoprotein cholesterol in hypercholesterolemic men: the lipid research clinics coronary primary prevention trial. Am J Clin Nutr. 1986 Oct;44(4):489-500. doi: 10.1093/ajcn/44.4.489.

Reference Type: BACKGROUND

PMID: 3532756 (View on PubMed)

Gordon DJ, Leon AS, Ekelund LG, Sopko G, Probstfield JL, Rubenstein C, Sheffield LT. Smoking, physical activity, and other predictors of endurance and heart rate response to exercise in asymptomatic hypercholesterolemic men. The Lipid Research Clinics Coronary Primary Prevention Trial. Am J Epidemiol. 1987 Apr;125(4):587-600. doi: 10.1093/oxfordjournals.aje.a114572.

Reference Type: BACKGROUND

PMID: 3826039 (View on PubMed)

Knoke JD, Hunninghake DB, Heiss G. Physiological markers of smoking and their relation to coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial. Arteriosclerosis. 1987 Sep-Oct;7(5):477-82. doi: 10.1161/01.atv.7.5.477.

Reference Type: BACKGROUND

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Gordon DJ, Hyde J, Trost DC, Whaley FS, Hannan PJ, Jacobs DR, Ekelund LG. Cyclic seasonal variation in plasma lipid and lipoprotein levels: the Lipid Research Clinics Coronary Primary Prevention Trial Placebo Group. J Clin Epidemiol. 1988;41(7):679-89. doi: 10.1016/0895-4356(88)90120-5.

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Wanis KN, Madenci AL, Hernan MA, Murray EJ. Adjusting for adherence in randomized trials when adherence is measured as a continuous variable: An application to the Lipid Research Clinics Coronary Primary Prevention Trial. Clin Trials. 2020 Oct;17(5):570-575. doi: 10.1177/1740774520920893. Epub 2020 May 15.

Reference Type: DERIVED

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Study Documents

Document Type: Individual Participant Data Set

NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.

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Document Type: Study Forms

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Other Identifiers

7

Identifier Type: -

Identifier Source: org_study_id