NCT00000512

Brief Summary

To compare the effects of two intensive lipid-lowering regimens with conventional therapy on coronary atherosclerosis as assessed by arteriography.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
146

participants targeted

Target at below P25 for phase_3 cardiovascular-diseases

Timeline
Completed

Started Jan 1984

Typical duration for phase_3 cardiovascular-diseases

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 1984

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 1989

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 1989

Completed
10.2 years until next milestone

First Submitted

Initial submission to the registry

October 27, 1999

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 28, 1999

Completed
Last Updated

December 3, 2015

Status Verified

December 1, 2015

Enrollment Period

5.6 years

First QC Date

October 27, 1999

Last Update Submit

December 1, 2015

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change in the Mean Severity of Proximal Stenosis

    At base line, the average percentage of stenosis caused by the worst lesion in each of nine proximal segments was 34 percent. On average, after 2 1/2 years of conventional therapy, this index of stenosis increased by 2.1 percentage points. By contrast, it decreased by 0.7 point during treatment with lovastatin and colestipol and by 0.9 with niacin and colestipol (P for trend \<0.003). Thus, at the end of the study, on average, these nine lesions were almost 3 percentage points less severe among patients treated intensively rather than conventionally. This difference represents almost 1/10 of the amount of disease present at base line (34 percent stenosis). The minimum diameter, an alternative index of the severity of disease, in the nine proximal lesions averaged 1.91 mm for all patients. It decreased (worsened) by 0.050 mm with conventional therapy but increased (improved) by 0.012 mm with lovastatin and colestipol and by 0.035 with niacin and colestipol (P for trend \<0.01).

    Baseline and 2.5 years of therapy.

Study Arms (3)

Niacin-Colestipol Group

EXPERIMENTAL

Colestipol was begun at a dose of 5 g three times a day with meals and increased to 10 g three times a day after 10 days, unless side effects delayed the increase. Psyllium hydrophic mucilloid (Metamucil) was provided if dietary bran was insufficient to control constipation. Niacin was started at 125 mg twice a day and gradually increased to 500 mg four times a day (with meals and at bedtime) at one month and 1 g four times a day at two months. If the LDL cholesterol level did not fall below 3.1 mmol per liter (120 mg per deciliter) after three months, the dose of niacin was increased to 1.5 g (three tablets) four times a day, but no further.

Drug: colestipolDrug: niacin

Lovastatin-Colestipol Group

EXPERIMENTAL

Colestipol was given as described above. Lovastatin was begun at a dose of 20 mg twice a day (in the morning and at bedtime). If the LDL cholesterol level did not fall below 3.1 mmol per liter after three months, the dose of lovastatin was increased to 40 mg twice a day.

Drug: lovastatinDrug: colestipol

Conventional-Therapy Group

PLACEBO COMPARATOR

Patients assigned to conventional therapy (the control regimen) received placebos for colestipol and for lovastatin, given as described above, unless their base-line LDL cholesterol level exceeded the 90th percentile for age. We felt obliged to provide such patients (43 percent of the group) with colestipol instead of its placebo. For purposes of blinding, the lovastatin placebo dose for a patient assigned to conventional therapy was doubled each time the lovastatin dose was doubled for a patient assigned to receive lovastatin and colestipol.

Drug: colestipolOther: Placebo for colestipolOther: Placebo for lovastatin

Interventions

Lovastatin was begun at a dose of 20 mg twice a day (in the morning and at bedtime). If the LDL cholesterol level did not fall below 3.1 mmol per liter after three months, the dose of lovastatin was increased to 40 mg twice a day.

Also known as: Mevacor
Lovastatin-Colestipol Group

Colestipol was begun at a dose of 5 g three times a day with meals and increased to 10 g three times a day after 10 days, unless side effects delayed the increase. Psyllium hydrophic mucilloid (Metamucil) was provided if dietary bran was insufficient to control constipation.

Also known as: Colestid
Conventional-Therapy GroupLovastatin-Colestipol GroupNiacin-Colestipol Group
niacinDRUG

Niacin was started at 125 mg twice a day and gradually increased to 500 mg four times a day (with meals and at bedtime) at one month and 1 g four times a day at two months. If the LDL cholesterol level did not fall below 3.1 mmol per liter (120 mg per deciliter) after three months, the dose of niacin was increased to 1.5 g (three tablets) four times a day, but no further.

Also known as: nicotinic acid
Niacin-Colestipol Group

Placebo for colestipol.

Conventional-Therapy Group

Placebo for lovastatin

Conventional-Therapy Group

Eligibility Criteria

Age18 Years - 62 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Men
  • Age 62 or younger
  • elevated apolipoprotein B levels
  • coronary atherosclerosis
  • family history of coronary heart disease.

You may not qualify if:

  • diabetes
  • severe hypertension
  • cancer
  • liver disease
  • thyroid disease
  • kidney disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (6)

  • Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990 Nov 8;323(19):1289-98. doi: 10.1056/NEJM199011083231901.

    PMID: 2215615BACKGROUND
  • Zhao XQ, Brown BG, Hillger L, Sacco D, Bisson B, Fisher L, Albers JJ. Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B. Circulation. 1993 Dec;88(6):2744-53. doi: 10.1161/01.cir.88.6.2744.

    PMID: 8252687BACKGROUND
  • Stewart BF, Brown BG, Zhao XQ, Hillger LA, Sniderman AD, Dowdy A, Fisher LD, Albers JJ. Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol. J Am Coll Cardiol. 1994 Mar 15;23(4):899-906. doi: 10.1016/0735-1097(94)90635-1.

    PMID: 8106695BACKGROUND
  • Brown BG, Hillger L, Zhao XQ, Poulin D, Albers JJ. Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease. Observations from the FATS Trial. Familial Atherosclerosis Treatment Study. Ann N Y Acad Sci. 1995 Jan 17;748:407-17; discussion 417-8. doi: 10.1111/j.1749-6632.1994.tb17337.x. No abstract available.

    PMID: 7695184BACKGROUND
  • Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). JAMA. 1995 Dec 13;274(22):1771-4.

    PMID: 7500507BACKGROUND
  • Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density. Circulation. 1999 Apr 20;99(15):1959-64. doi: 10.1161/01.cir.99.15.1959.

    PMID: 10208998BACKGROUND

MeSH Terms

Conditions

Cardiovascular DiseasesCoronary Artery DiseaseCoronary DiseaseHeart DiseasesMyocardial Ischemia

Interventions

LovastatinColestipolNiacin

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

NaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsPolyaminesAminesPolymersMacromolecular SubstancesBiomedical and Dental MaterialsManufactured MaterialsTechnology, Industry, and AgricultureNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • B. Greg Brown, M.D., Ph.D

    University of Washington

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research Professor of Medicine

Study Record Dates

First Submitted

October 27, 1999

First Posted

October 28, 1999

Study Start

January 1, 1984

Primary Completion

August 1, 1989

Study Completion

August 1, 1989

Last Updated

December 3, 2015

Record last verified: 2015-12