CARotid plaqUe StabilizatiOn and Regression With Evolocumab: the CARUSO Study
Trial Snapshot
- Phase
- Phase 4
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- Morphological carotid plaque stabilization
Study Overview
Brief Summary
The CARUSO trial aims at investigating the efficacy of evolocumab in promoting carotid plaque morphological stabilization and regression as compared to traditional lipid lowering therapy (LLT). Primary end-point of the study is the superiority of evolocumab on top of ongoing LLT versus ongoing LLT in carotid plaque morphological stabilization and regression at 6 and 12 months, respectively. Secondary end-points are: LDL-Cholesterol (LDL-C) absolute and percentage changes in the two groups at 12 month follow-up, and adverse cerebrovascular and cardiac events at 12 and 24 months
Detailed Description
Optimal lipid-lowering therapy (LLT) is a mainstay for the therapeutic management of atherosclerotic vascular disease. Cardiac and cerebrovascular adverse events and progression of atherosclerosis are, indeed, reduced in proportion to the achieved LDL cholesterol (LDL-C) levels.In addition, regression of atherosclerotic plaques with optimal LLT has been observed. However, optimal LLT with statin and ezetimibe, might be limited by the onset of adverse effects (i.e. disabling myalgias, diarrhea) with are usually dose -dependent, and the maximum tolerated statin dose might be insufficient to reach the recommended LDL-C goals. The advent of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) has allowed the achievement of very low LDL-C levels, and the fulfillment of the recommended LDL-C targets. However, while the experience with PCSK9i in patients with coronary artery disease has been wide, and coronary plaque regression has been documented, little is known regarding carotid plaque regression following therapy with PCSK9i. Only a few case reports have been published, and no observational study has been carried out so far. Furthermore, morphological carotid plaque stabilization has a prognostic role, and the possibility of its early achievement with PCSK9i may be relevant, especially in the context of percutaneous or surgical carotid interventions.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Investigator, Outcomes Assessor)
Masking Description
Single blinded study
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •asymptomatic patients with uni- or bilateral carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dL despite ongoing lipid lowering therapy
Exclusion Criteria
- •age <18 or ≥81 years old
- •known intolerance to evolocumab
- •ongoing or previous treatment with PCSK9i
- •prior stroke or transient ischemic attack
- •total carotid occlusion
- •major active infection or major hematologic, renal, hepatic, or endocrine dysfunction
- •malignancy with life expectancy below 24 months
- •failure to sign informed consent
Arms & Interventions
Evolocumab
Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy
Intervention: Evolocumab (Drug)
Evolocumab
Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy
Intervention: lipid-lowering therapy (LLT) (Other)
Standard
No further treatment besides optimal lipid-lowering therapy will be administered
Intervention: lipid-lowering therapy (LLT) (Other)
Outcomes
Primary Outcomes
Morphological carotid plaque stabilization
Time Frame: Six months
Morphological stabilization of the carotid plaque evaluated with Carotid duplex ultra-sonography
Carotid plaque regression
Time Frame: 12 months
Carotid plaque regression evaluated with Carotid duplex ultra-sonography and defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared to baseline.
Secondary Outcomes
- Changes of LDL-C(12 months)
- Major adverse cerebrovascular events(12 and 24 months)
Investigators
Tiziana Claudia Aranzulla
MD, MSc
Azienda Ospedaliera Ordine Mauriziano di Torino