CARotid plaqUe StabilizatiOn and Regression With Evolocumab. (CARUSO)

Azienda Ospedaliera Ordine Mauriziano di Torino

Status and phase: Unknown; Phase 4

Conditions: Carotid Artery Disease

Treatments: Drug: Evolocumab; Other: lipid-lowering therapy (LLT)

Study type: Interventional

Funder types: Other

Identifiers

NCT04730973

2020-005663-31

Details and patient eligibility

About

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

Full 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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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130 participants in 2 patient groups, including a placebo group

Evolocumab

Active Comparator group

Description:

Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy

Treatment:

Other: lipid-lowering therapy (LLT)

Drug: Evolocumab

Standard

Placebo Comparator group

Description:

No further treatment besides optimal lipid-lowering therapy will be administered

Treatment:

Other: lipid-lowering therapy (LLT)