Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000469
Status:
COMPLETED
Last Update Posted:
2016-05-13
First Post:
1999-10-27
Brief Title:
Asymptomatic Carotid Artery Plaque Study ACAPS
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2000-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine whether warfarin or lovastatin alone or in combination retarded the progression of atherosclerotic plaques in the carotid arteries of high risk individuals with asymptomatic carotid stenosis Also to determine if a full scale trial was feasible
Detailed Description:
BACKGROUND
At the present time atherosclerosis of the major extracranial arteries to the brain is considered the cause of most strokes Early intervention and stroke prevention utilized anti-coagulants such as coumadin and heparin Results were largely equivocal due to the diverse nature of the underlying pathogenesis and due to problems that offset potential benefit Emphasis gradually switched to aspirin and to other platelet anti-aggregant drugs because of mounting evidence that micro-emboli were a major element in transient ischemic attacks Several studies have examined the potential benefit of aspirin in stroke prevention The exact dose of aspirin that was maximally beneficial with minimal side effects was not completely established There was evidence that low dose aspirin was as effective as higher doses The American College of Chest Physicians ACCP made recommendations that if aspirin were issued as a primary anti-thrombotic agent the dose should be 325 mg daily except in patients with cerebrovascular disease in whom the lowest beneficial dose appeared to be one gram per day The ACCP also pointed out that the risk of bleeding was substantially greater in patients with ischemic cerebrovascular disease and venous thromboembolism than in other high risk groups requiring anticoagulation It advised that anticoagulant therapy was not needed but that aspirin might be given at 325 mg per day
Lovastatin is a fungal metabolite that inhibits 3-hydroxy 3-methyl glutaryl coenzyme A reductase the rate-limiting enzyme of cholesterol biosynthesis in human cells including the liver Inhibition of this pathway causes the cells to increase their low density lipoprotein receptor numbers to compensate causing a reduction in circulating low density lipoprotein levels with a consequent drop in circulating plasma cholesterol levels The drug also raises high density lipoprotein levels significantly A favorable outcome of the trial will have major public health implications for the prevention and control of atherosclerosis and its complications
DESIGN NARRATIVE
Randomized double-blind factorial design In this multicenter study patients were assigned to one of four drug combination groups active lovastatinactive warfarin active lovastatinwarfarin placebo lovastatin placeboactive warfarin and lovastatin placebowarfarin placebo Daily aspirin was recommended for everyone Ultrasound was performed for screening at baseline and semiannually thereafter Lipid profiles were obtained at screening at baseline monthly for the first three months at six months and annually thereafter with beta quantification at baseline Recruitment began in the tenth month of the trial and continued for one year ending in September 1990 Treatment continued through the 51st month Average treatment period was 27 years Subjects were offered a dietary regimen for three months prior to receiving any drug therapy Only those individuals whose lipid levels did not fall below a certain point continued in dietary intervention The primary outcome measure was the three year change in mean maximum intimal-medial thickness IMT in twelve walls of the carotid arteries Secondary outcomes included change in single maximum IMT and incidence of major cardiovascular events
In 1995 an R03 was awarded to Mark Espeland to extend analyses of the carotid B-mode ultrasound data through August 1998
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
At the present time atherosclerosis of the major extracranial arteries to the brain is considered the cause of most strokes Early intervention and stroke prevention utilized anti-coagulants such as coumadin and heparin Results were largely equivocal due to the diverse nature of the underlying pathogenesis and due to problems that offset potential benefit Emphasis gradually switched to aspirin and to other platelet anti-aggregant drugs because of mounting evidence that micro-emboli were a major element in transient ischemic attacks Several studies have examined the potential benefit of aspirin in stroke prevention The exact dose of aspirin that was maximally beneficial with minimal side effects was not completely established There was evidence that low dose aspirin was as effective as higher doses The American College of Chest Physicians ACCP made recommendations that if aspirin were issued as a primary anti-thrombotic agent the dose should be 325 mg daily except in patients with cerebrovascular disease in whom the lowest beneficial dose appeared to be one gram per day The ACCP also pointed out that the risk of bleeding was substantially greater in patients with ischemic cerebrovascular disease and venous thromboembolism than in other high risk groups requiring anticoagulation It advised that anticoagulant therapy was not needed but that aspirin might be given at 325 mg per day
Lovastatin is a fungal metabolite that inhibits 3-hydroxy 3-methyl glutaryl coenzyme A reductase the rate-limiting enzyme of cholesterol biosynthesis in human cells including the liver Inhibition of this pathway causes the cells to increase their low density lipoprotein receptor numbers to compensate causing a reduction in circulating low density lipoprotein levels with a consequent drop in circulating plasma cholesterol levels The drug also raises high density lipoprotein levels significantly A favorable outcome of the trial will have major public health implications for the prevention and control of atherosclerosis and its complications
DESIGN NARRATIVE
Randomized double-blind factorial design In this multicenter study patients were assigned to one of four drug combination groups active lovastatinactive warfarin active lovastatinwarfarin placebo lovastatin placeboactive warfarin and lovastatin placebowarfarin placebo Daily aspirin was recommended for everyone Ultrasound was performed for screening at baseline and semiannually thereafter Lipid profiles were obtained at screening at baseline monthly for the first three months at six months and annually thereafter with beta quantification at baseline Recruitment began in the tenth month of the trial and continued for one year ending in September 1990 Treatment continued through the 51st month Average treatment period was 27 years Subjects were offered a dietary regimen for three months prior to receiving any drug therapy Only those individuals whose lipid levels did not fall below a certain point continued in dietary intervention The primary outcome measure was the three year change in mean maximum intimal-medial thickness IMT in twelve walls of the carotid arteries Secondary outcomes included change in single maximum IMT and incidence of major cardiovascular events
In 1995 an R03 was awarded to Mark Espeland to extend analyses of the carotid B-mode ultrasound data through August 1998
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL038194 | NIH | None | httpsreporternihgovquickSearchR01HL038194 |