- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00000512
Familial Atherosclerosis Treatment Study (FATS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
BACKGROUND:
For several decades, clinical trials have addressed the question of whether treatment of hyperlipidemia reduces the risk of cardiovascular events. Substantial evidence supports the idea that cardiovascular benefits are related to the degree of reduction in low-density lipoprotein cholesterol level and perhaps to the degree of increase in the high-density lipoprotein cholesterol level. In these trials, changes in lipid levels have usually been small and the overall clinical benefits have been limited. The appearance in the 1980s of more effective treatments for hyperlipidemia, new arteriographic methods for assessing atherosclerosis, and new insights into atherogenesis permitted an objective investigation into whether the progression of atherosclerosis was retarded or reversed by lipid-lowering agents.
The clinical trial was supported by a subproject within a program project grant.
DESIGN NARRATIVE:
Randomized, double-blind, placebo-controlled. Baseline arteriograms were performed and fasting lipid samples drawn before heparinization. Patients were stratified for age below 45 years, cigarette smoking within the previous month, and lipid patterns including familial hypercholesterolemia and triglyceride levels. Patients were given dietary counseling and randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day): or conventional therapy with placebo (or colestipol if the LDL cholesterol level was elevated). The primary endpoint was a measure of change in the severity of disease in the proximal coronary arteries as measured by quantitative arteriography.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men
- Age 62 or younger
- elevated apolipoprotein B levels
- coronary atherosclerosis
- family history of coronary heart disease.
Exclusion Criteria:
- diabetes
- severe hypertension
- cancer
- liver disease
- thyroid disease
- kidney disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Niacin-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.
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.
|
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.
Other Names:
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.
Other Names:
|
Experimental: Lovastatin-Colestipol Group
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.
|
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.
Other Names:
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.
Other Names:
|
Placebo Comparator: Conventional-Therapy Group
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.
|
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.
Other Names:
Placebo for colestipol.
Placebo for lovastatin
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the Mean Severity of Proximal Stenosis
Time Frame: Baseline and 2.5 years of therapy.
|
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.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: B. Greg Brown, M.D., Ph.D, University of Washington
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Vascular Diseases
- Arterial Occlusive Diseases
- Heart Diseases
- Coronary Artery Disease
- Myocardial Ischemia
- Coronary Disease
- Cardiovascular Diseases
- Ischemia
- Arteriosclerosis
- Atherosclerosis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Enzyme Inhibitors
- Antimetabolites
- Micronutrients
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Vitamins
- Vitamin B Complex
- Sequestering Agents
- Nicotinic Acids
- Niacin
- Lovastatin
- L 647318
- Dihydromevinolin
- Colestipol
Other Study ID Numbers
- 28764-W
- P01HL030086 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myocardial Ischemia
-
Recardio, Inc.CompletedAcute Myocardial Infarction | STEMI - ST Elevation Myocardial Infarction | Acute Myocardial IschemiaNetherlands, Hungary, Austria, Poland, Belgium
-
University of Roma La SapienzaCompletedRosuvastatin in Preventing Myonecrosis in Elective Percutaneous Coronary Interventions (PCIs) (ROMA)Periprocedural Myocardial NecrosisItaly
-
Lokien van NunenMaquet Cardiovascular; Stichting Toegepaste Wetenschappen (project number 11052)CompletedAcute Myocardial Infarction | Persisting Ischemia | No ReflowNetherlands
-
Tomsk National Research Medical Center of the Russian...CompletedMyocardial Infarction | Myocardial Injury | STEMI | Myocardial NecrosisRussian Federation
-
University Hospital, ToulouseThoratec CorporationWithdrawnChronic Myocardial IschemiaFrance
-
Tehran University of Medical SciencesRecruitingMyocardial Infarction | Myocardial Ischemia | Myocardial StunningIran, Islamic Republic of
-
University of TurkuTurku University HospitalEnrolling by invitationMyocardial Infarction | Myocardial InjuryFinland
-
EZUS-LYON 1Active, not recruiting
-
Samsung Medical CenterCompletedMyocardial Infarction | Myocardial ReperfusionKorea, Republic of
-
Gennaro SardellaCompletedAssess the Periprocedural Myocardial NecrosisItaly
Clinical Trials on colestipol
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedMyocardial Ischemia | Heart Diseases | Cardiovascular Diseases | Cerebrovascular Disorders | Coronary Disease | Arterial Occlusive Diseases | Atherosclerosis | Carotid Artery Diseases | Coronary Arteriosclerosis | Cerebral Arteriosclerosis
-
Brigham and Women's HospitalCompleted
-
Tuscaloosa Research & Education Advancement CorporationAmerican Society of Health-System Pharmacists Research and Education FoundationCompletedHypercholesterolemia | HyperlipidemiaUnited States
-
Derrick Scott RobertsonUniversity of South Florida; Genzyme, a Sanofi CompanyTerminatedHealthy Volunteers | Teriflunomide EliminationUnited States
-
Puma Biotechnology, Inc.CompletedEarly Stage HER2+ Breast CancerSpain, United States, France, Australia, Germany, Austria, Canada