Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00120289
Status:
TERMINATED
Last Update Posted:
2016-04-06
First Post:
2005-07-06
Brief Title:
Niacin Plus Statin to Prevent Vascular Events
Sponsor:
Axio Research LLC
Organization:
Axio Research LLC
Study Overview
Official Title:
AIM HIGH Niacin Plus Statin to Prevent Vascular Events
Status:
TERMINATED
Status Verified Date:
2016-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
AIM-HIGH was stopped on the recommendation of the DSMB because of lack of efficacy of niacin in preventing primary outcome events
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether raising good cholesterol with a drug based on the vitamin niacin while lowering bad cholesterol with a statin drug can prevent more heart disease than the statin alone
Detailed Description:
BACKGROUND
Coronary heart disease CHD remains the leading cause of death and disability in the Western world with approximately 126 million individuals in the United States having a history of myocardial infarction MI angina or both There is mounting evidence that conventional therapies aimed at traditional risk factors have not optimized clinical outcomes For example in the Heart Protection Study with 20536 subjects the 5-year risk of a first major vascular event nonfatal MI or CHD death stroke or coronary or noncoronary revascularization among placebo-treated patients was 25 Treatment with simvastatin reduced this risk to 20 over 5 years which would project out to a 10-year risk of 40 The National Cholesterol Education Program Adult Treatment Panel III considers high risk or CHD equivalent a 10-year risk of an event greater than 20 Even among patients entering the study with baseline low density lipoprotein cholesterol LDL-C already near or at goal ie LDL-C less than 116 mgdL and who achieved a mean on-trial LDL-C of 70 mgdL with simvastatin the 5-year risk of an event was still 18 projecting to a 10-year risk of 36 This residual and unacceptably high risk is likely due to the increasing prevalence of obesity type II diabetes mellitus and the metabolic syndrome These disorders are typically accompanied by a constellation of abnormalities that include impaired glycemic control hypertension procoagulant and inflammatory states and atherogenic dyslipidemia The latter includes a wide spectrum of lipid abnormalities low HDL-C high triglycerides and triglyceride-rich remnant lipoproteins and a preponderance of small dense highly-oxidizable LDL particles
Conventional LDL-C-focused therapies are not effective in targeting this type of dyslipidemia Evidence that therapy directed at atherogenic dyslipidemia among patients with CHD can lower outcomes was shown with gemfibrozil in the VA-HIT trial which showed a 22 to 24 cardiovascular CV event reduction by raising HDL-C by an average of 6 and lowering triglycerides by an average of 31 Niacin is an even more effective agent for simultaneously raising HDL-C and lowering triglycerides and levels of small dense LDL and holds the most promise among existing therapies for substantial risk reduction in this population when added to a statin This was demonstrated in the HDL Atherosclerosis Treatment Study HATS trial in which atherosclerosis progression was virtually halted and CV events were reduced by 60 to 90 using combined niacin plus statin therapy
DESIGN NARRATIVE
AIM-HIGH is a multicenter randomized double-blind parallel-group controlled clinical trial designed to test whether the drug combination of extended release niacin plus simvastatin is superior to simvastatin alone at comparable levels of on-treatment LDL-C for delaying the time to a first major CV disease outcome over a 4-year median follow-up in patients with atherogenic dyslipidemia Prior clinical trials have found only 25 to 35 CV risk reduction using statin monotherapy ie event rate 23 to 34 of placebo rate The study is needed to confirm whether statin-niacin combination therapy designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C will provide a more substantial greater than 50 reduction of CV events Epidemiologic studies confirm the high prevalence of atherogenic dyslipidemia and its impact on CV event rates Preliminary clinical trials suggest that targeting these factors with dyslipidemic therapy will reduce CV events The study will enroll an estimated 3300 men and women more than 45 years old at high risk of recurrent CV events by virtue of having established CV disease together with the two dyslipidemic elements of metabolic syndrome low HDL-cholesterol HDL-C less than or equal to 40 mgdl and high triglycerides TG greater than or equal to 150 mgdl The study specifically aims to test this hypothesis for the primary composite clinical end point of CHD death nonfatal MI ischemic stroke hospitalization for acute coronary syndrome with objective evidence of ischemia troponin-positive or ST-segment deviation or symptom-driven coronary or cerebral revascularization Secondary end points include the composite of CHD death nonfatal MI ischemic stroke or hospitalization for high-risk acute coronary syndrome the composite of CHD death nonfatal MI or ischemic stroke and cardiovascular mortality
Coronary heart disease CHD remains the leading cause of death and disability in the Western world with approximately 126 million individuals in the United States having a history of myocardial infarction MI angina or both There is mounting evidence that conventional therapies aimed at traditional risk factors have not optimized clinical outcomes For example in the Heart Protection Study with 20536 subjects the 5-year risk of a first major vascular event nonfatal MI or CHD death stroke or coronary or noncoronary revascularization among placebo-treated patients was 25 Treatment with simvastatin reduced this risk to 20 over 5 years which would project out to a 10-year risk of 40 The National Cholesterol Education Program Adult Treatment Panel III considers high risk or CHD equivalent a 10-year risk of an event greater than 20 Even among patients entering the study with baseline low density lipoprotein cholesterol LDL-C already near or at goal ie LDL-C less than 116 mgdL and who achieved a mean on-trial LDL-C of 70 mgdL with simvastatin the 5-year risk of an event was still 18 projecting to a 10-year risk of 36 This residual and unacceptably high risk is likely due to the increasing prevalence of obesity type II diabetes mellitus and the metabolic syndrome These disorders are typically accompanied by a constellation of abnormalities that include impaired glycemic control hypertension procoagulant and inflammatory states and atherogenic dyslipidemia The latter includes a wide spectrum of lipid abnormalities low HDL-C high triglycerides and triglyceride-rich remnant lipoproteins and a preponderance of small dense highly-oxidizable LDL particles
Conventional LDL-C-focused therapies are not effective in targeting this type of dyslipidemia Evidence that therapy directed at atherogenic dyslipidemia among patients with CHD can lower outcomes was shown with gemfibrozil in the VA-HIT trial which showed a 22 to 24 cardiovascular CV event reduction by raising HDL-C by an average of 6 and lowering triglycerides by an average of 31 Niacin is an even more effective agent for simultaneously raising HDL-C and lowering triglycerides and levels of small dense LDL and holds the most promise among existing therapies for substantial risk reduction in this population when added to a statin This was demonstrated in the HDL Atherosclerosis Treatment Study HATS trial in which atherosclerosis progression was virtually halted and CV events were reduced by 60 to 90 using combined niacin plus statin therapy
DESIGN NARRATIVE
AIM-HIGH is a multicenter randomized double-blind parallel-group controlled clinical trial designed to test whether the drug combination of extended release niacin plus simvastatin is superior to simvastatin alone at comparable levels of on-treatment LDL-C for delaying the time to a first major CV disease outcome over a 4-year median follow-up in patients with atherogenic dyslipidemia Prior clinical trials have found only 25 to 35 CV risk reduction using statin monotherapy ie event rate 23 to 34 of placebo rate The study is needed to confirm whether statin-niacin combination therapy designed to target a wider spectrum of dyslipidemic factors in addition to LDL-C will provide a more substantial greater than 50 reduction of CV events Epidemiologic studies confirm the high prevalence of atherogenic dyslipidemia and its impact on CV event rates Preliminary clinical trials suggest that targeting these factors with dyslipidemic therapy will reduce CV events The study will enroll an estimated 3300 men and women more than 45 years old at high risk of recurrent CV events by virtue of having established CV disease together with the two dyslipidemic elements of metabolic syndrome low HDL-cholesterol HDL-C less than or equal to 40 mgdl and high triglycerides TG greater than or equal to 150 mgdl The study specifically aims to test this hypothesis for the primary composite clinical end point of CHD death nonfatal MI ischemic stroke hospitalization for acute coronary syndrome with objective evidence of ischemia troponin-positive or ST-segment deviation or symptom-driven coronary or cerebral revascularization Secondary end points include the composite of CHD death nonfatal MI ischemic stroke or hospitalization for high-risk acute coronary syndrome the composite of CHD death nonfatal MI or ischemic stroke and cardiovascular mortality
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U01HL081649 | NIH | None | None |
| U01HL081616 | NIH | None | httpsreporternihgovquickSearchU01HL081616 |