Lipid Research Clinics Coronary Primary Prevention Trial (CPPT)

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000488

Collaborator

(none)

196

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Coronary Disease Heart Diseases Myocardial Ischemia	Drug: cholestyramine Behavioral: diet, fat-restricted	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

Study Start Date :

Jun 1, 1973

Actual Study Completion Date :

Oct 1, 1989

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 59 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

: Francois Abboud, University of Iowa
: Elizabeth Barrett-Connor, University of California, San Diego
: Reagan Bradford, Oklahoma Medical Research Foundation
: Marilyn Buzzard, University of Minnesota
: Gerald Cooper, Centers for Disease Control and Prevention
: John Farquhar, Stanford University
: Ivan Frantz, University of Minnesota
: Anne Goldberg, Washington University School of Medicine
: Frank Ibbott, Bio-Science Laboratories
: William, Insull, Baylor College of Medicine
: Robert Knoop, University of Washington
: Peter Kwiterovich, Johns Hopkins University
: John LaRosa, George Washington University
: J. Little, University of Toronto
: L. Sheffield, University of Alabama at Birmingham
: Dennis Sprecher, University of Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00000488

Other Study ID Numbers:

First Posted:

Oct 28, 1999

Last Update Posted:

Apr 14, 2016

Last Verified:

Apr 1, 2012

Additional relevant MeSH terms:

Cardiovascular Diseases

Study Results

No Results Posted as of Apr 14, 2016