CARotid plaqUe StabilizatiOn and Regression With Evolocumab. (CARUSO)

CARotid plaqUe StabilizatiOn and Regression With Evolocumab: the CARUSO Study

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

Study Overview

• Status: Recruiting
• Conditions: Carotid Artery Disease
• Intervention / Treatment: Drug: Evolocumab; Other: lipid-lowering therapy (LLT)

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 Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tiziana Claudia Aranzulla, MD; Phone Number: +390115085038; Email: taranzulla@mauriziano.it

Study Locations

• Italy
  • Piedmont
    • Torino, Piedmont, Italy, 10134
      • Recruiting
      • Azienda Ospedaliera Ordine Mauriziano di Torino
      • Contact: Tiziana Claudia Aranzulla, MD; Phone Number: +393383145483; Email: aranzulla.tiziana@gmail.com
      • Contact: Irene Borsotti; Phone Number: +390115082222; Email: lborsotti@mauriziano.it
      • Principal Investigator: Tiziana Claudia Aranzulla, MD, MSc
      • Sub-Investigator: Salvatore Piazza, MD
      • Sub-Investigator: Andrea Ricotti, MD
      • Sub-Investigator: Giuseppe Musumeci, MD
      • Sub-Investigator: Andrea Gaggiano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Evolocumab; Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy	Drug: Evolocumab; Evolocumab 140 mg s.c. every two weeks on top of optimal lipid lowering therapy; Other Names: Repatha; Other: lipid-lowering therapy (LLT); lipid-lowering therapy (LLT)
PLACEBO_COMPARATOR: Standard; No further treatment besides optimal lipid-lowering therapy will be administered	Other: lipid-lowering therapy (LLT); lipid-lowering therapy (LLT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphological carotid plaque stabilization	Morphological stabilization of the carotid plaque evaluated with Carotid duplex ultra-sonography	Six months
Carotid plaque regression	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of LDL-C	Absolute changes of LDL-C	12 months
Major adverse cerebrovascular events	All-cause mortality, cardiovascular mortality, stroke, myocardial infarction, any coronary or peripheral revascularization	12 and 24 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Ordine Mauriziano di Torino
• Investigators: Principal Investigator: Tiziana Claudia Aranzulla, MD, A.O. Ordine Mauriziano di Torino

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2021
• Primary Completion (ANTICIPATED): March 31, 2022
• Study Completion (ANTICIPATED): March 31, 2022

Study Registration Dates

• First Submitted: January 24, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (ACTUAL): January 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carotid Artery Diseases; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 2020-005663-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No