Ignite Creation Date:
2024-07-17 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06494501
Status:
RECRUITING
Last Update Posted:
2024-07-10
First Post:
2024-06-23
Brief Title:
The Prevent Coronary Artery Disease Trial
Sponsor:
Icahn School of Medicine at Mount Sinai
Organization:
Icahn School of Medicine at Mount Sinai
Study Overview
Official Title:
The Prevent Coronary Artery Disease Trial
Status:
RECRUITING
Status Verified Date:
2024-07
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:
PRECAD
Brief Summary:
Despite increasing evidence that exposure to cardiovascular risk factors CVRF at an early age increases the prevalence of subclinical atherosclerosis and is associated with a greater risk of cardiovascular events later in life there is a lack of randomized trial evidence to support primary prevention strategies in adults aged 30-50 years The researchers have designed a randomized controlled trial to evaluate whether strict control of CVRF in young adults without known cardiovascular disease will reduce the progression of total atherosclerosis burden a surrogate endpoint for symptomatic cardiovascular disease compared with usual care
The researchers propose a randomized controlled trial enrolling 1600 healthy young adults who meet the inclusion criteria and who do not meet any exclusion criteria Eligible study participants will be randomized in a 11 ratio to either the intervention group active treatment strategy or to the control group guideline-directed medical therapy Randomization will be stratified by the presence or absence of atherosclerotic plaque in vascular ultrasound
The researchers propose a randomized controlled trial enrolling 1600 healthy young adults who meet the inclusion criteria and who do not meet any exclusion criteria Eligible study participants will be randomized in a 11 ratio to either the intervention group active treatment strategy or to the control group guideline-directed medical therapy Randomization will be stratified by the presence or absence of atherosclerotic plaque in vascular ultrasound
Detailed Description:
Atherosclerotic cardiovascular disease ASCVD is the most common cause of death in the world and contributes importantly to the majority of the worlds deaths Substantial data suggest that maintaining optimal population serum low density lipoprotein cholesterol LDL-C starting early in life has the potential to lower the risk of incident ASCVD However this strategy of early initiation of LDL-C lowering therapies would represent a major paradigm shift from current guideline-based practice Widespread acceptance and implementation of this approach in the medical community necessary to gain a population benefit will require a randomized clinical trial demonstrating benefit Thus the researchers will begin a trial PRECAD that evaluates LDL-C lowering in the early adult years through measurements of subclinical atherosclerosis
The significance of subclinical atherosclerosis has been established in population-based studies In a cohort of 4000 subjects between 40-54 years the Progression of Early Atherosclerosis PESA study showed that 63 of the asymptomatic participants presented subclinical atherosclerosis and that it progresses with time Subclinical atherosclerosis was associated with cardiovascular events along 10 years of follow-up in the CAFES-CAVE study Similar findings were reported from the BioImage study in the HRP cohort have shown that presence of plaque even in asymptomatic phases improved risk reclassification and was independently associated with adverse cardiovascular events in long-term follow-up Hence demonstrating prevention of atherosclerosis progression is strongly suggestive of future clinical benefit
LDL-C even at levels currently considered normal is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major cardiovascular risk factors These findings support more effective LDL-C lowering for primary prevention
Research from multiple observational cohort studies has shown that risk of cardiovascular disease increases with increased exposure to elevated LDL-C independent of other risk factors in a concentration-dependent fashion In the CARDIA study which enrolled adults aged 18- 30 years with a median 16-year follow-up incident cardiovascular disease risk increased as accumulation of exposure to LDL-C increased Further LDL-C level predicts progression of subclinical atherosclerosis measured by the PESA score and subclinical atherosclerosis progression predicts CHD For the composite event of all-cause death nonfatal myocardial infarction or nonfatal stroke the updated event outcomes have the following distribution across PESA score categories no disease n1536 number of events 10 065 focal n875 number of events 8 091 intermediate n1112 number of events 13 117 generalized n547 number events 13 238 These preliminary results although unpublished provide a rationale that higher PESA score portends a higher clinical event rate
Under a different imaging score of atherosclerosis burden a similar association between atherosclerosis burden and clinical event rate has also been observed in the preliminary unpublished data of the BioImage Study The connection between the atherosclerosis burden and incident CHD offers a surrogate endpoint for CHD that will progress sooner permitting a much shorter trial that will convincingly assess the primary prevention benefit of maintaining low LDL-C beginning early in adult life
Strict diet and aggressive lifestyle changes are associated with LDL-C reduction but adherence is generally poor In the last year the World Health Organization has included new strategies such as the polypill in its list of essential medicines in response to the limitation that lack of adherence places on the management of patients particularly in the setting of prevention
Particularly difficult is to guarantee adherence in young populations due to the absence of risk awareness Thus new strategies should be implemented to guarantee adherence in these population subgroups Inclisiran is a small interfering RNA administered twice-yearly after the initial and 3-month doses by a health care professional via subcutaneous injection that decreases production of proprotein convertase subtilisin-lexin type 9 PCSK9 in the liver to low LDL-C levels This treatment has been shown as a safe effective and well tolerated in a diverse population and could represent a great opportunity to increase adherence in the setting of primary prevention
A population requiring special attention are patients with familial hypercholesterolemia FH LDL-C is 2 times higher in patients with heterozygous FH and 4-5 times higher in patients with homozygous familial hypercholesterolemia compared to the general population Based on the high baseline LDL-C levels in FH patients lowering of LDL-C may not be achieved with statins alone Inclisiran has also been shown effective in adults with FH who are treated with maximally tolerated statin therapy with or without ezetimibe
The hypothesis is that compared to usual care maintaining LDL-C below 55 mgdL beginning in the early adult years 30-50 years in addition to a strict control of other risk factors will reduce progression of total atherosclerosis burden
The significance of subclinical atherosclerosis has been established in population-based studies In a cohort of 4000 subjects between 40-54 years the Progression of Early Atherosclerosis PESA study showed that 63 of the asymptomatic participants presented subclinical atherosclerosis and that it progresses with time Subclinical atherosclerosis was associated with cardiovascular events along 10 years of follow-up in the CAFES-CAVE study Similar findings were reported from the BioImage study in the HRP cohort have shown that presence of plaque even in asymptomatic phases improved risk reclassification and was independently associated with adverse cardiovascular events in long-term follow-up Hence demonstrating prevention of atherosclerosis progression is strongly suggestive of future clinical benefit
LDL-C even at levels currently considered normal is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major cardiovascular risk factors These findings support more effective LDL-C lowering for primary prevention
Research from multiple observational cohort studies has shown that risk of cardiovascular disease increases with increased exposure to elevated LDL-C independent of other risk factors in a concentration-dependent fashion In the CARDIA study which enrolled adults aged 18- 30 years with a median 16-year follow-up incident cardiovascular disease risk increased as accumulation of exposure to LDL-C increased Further LDL-C level predicts progression of subclinical atherosclerosis measured by the PESA score and subclinical atherosclerosis progression predicts CHD For the composite event of all-cause death nonfatal myocardial infarction or nonfatal stroke the updated event outcomes have the following distribution across PESA score categories no disease n1536 number of events 10 065 focal n875 number of events 8 091 intermediate n1112 number of events 13 117 generalized n547 number events 13 238 These preliminary results although unpublished provide a rationale that higher PESA score portends a higher clinical event rate
Under a different imaging score of atherosclerosis burden a similar association between atherosclerosis burden and clinical event rate has also been observed in the preliminary unpublished data of the BioImage Study The connection between the atherosclerosis burden and incident CHD offers a surrogate endpoint for CHD that will progress sooner permitting a much shorter trial that will convincingly assess the primary prevention benefit of maintaining low LDL-C beginning early in adult life
Strict diet and aggressive lifestyle changes are associated with LDL-C reduction but adherence is generally poor In the last year the World Health Organization has included new strategies such as the polypill in its list of essential medicines in response to the limitation that lack of adherence places on the management of patients particularly in the setting of prevention
Particularly difficult is to guarantee adherence in young populations due to the absence of risk awareness Thus new strategies should be implemented to guarantee adherence in these population subgroups Inclisiran is a small interfering RNA administered twice-yearly after the initial and 3-month doses by a health care professional via subcutaneous injection that decreases production of proprotein convertase subtilisin-lexin type 9 PCSK9 in the liver to low LDL-C levels This treatment has been shown as a safe effective and well tolerated in a diverse population and could represent a great opportunity to increase adherence in the setting of primary prevention
A population requiring special attention are patients with familial hypercholesterolemia FH LDL-C is 2 times higher in patients with heterozygous FH and 4-5 times higher in patients with homozygous familial hypercholesterolemia compared to the general population Based on the high baseline LDL-C levels in FH patients lowering of LDL-C may not be achieved with statins alone Inclisiran has also been shown effective in adults with FH who are treated with maximally tolerated statin therapy with or without ezetimibe
The hypothesis is that compared to usual care maintaining LDL-C below 55 mgdL beginning in the early adult years 30-50 years in addition to a strict control of other risk factors will reduce progression of total atherosclerosis burden
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None