Clinical trial NCT04730973: CARotid plaqUe StabilizatiOn and Regression With Evolocumab.
Official title: CARotid plaqUe StabilizatiOn and Regression With Evolocumab: the CARUSO Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Carotid Artery Disease
Lead sponsor: Azienda Ospedaliera Ordine Mauriziano di Torino
Sponsor class: OTHER
First posted: 2021-01-29
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled study
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Morphological carotid plaque stabilization
timeFrame: Six months
measure: Carotid plaque regression
timeFrame: 12 months
Secondary outcomes:
measure: Changes of LDL-C
timeFrame: 12 months
measure: Major adverse cerebrovascular events
timeFrame: 12 and 24 months
Other outcomes:
Locations:
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
state: Piedmont
Study officials:
affiliation: A.O. Ordine Mauriziano di Torino
name: Tiziana Claudia Aranzulla, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aranzulla TC, Piazza S, Ricotti A, Musumeci G, Gaggiano A. CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study. Catheter Cardiovasc Interv. 2021 Jul 1;98(1):E115-E121. doi: 10.1002/ccd.29743. Epub 2021 Apr 24.