Carotid Artery DiseasePhase 4CARUSONCT04730973
CARotid plaqUe StabilizatiOn and Regression With Evolocumab.
A Phase 4 study testing Evolocumab and lipid-lowering therapy (LLT) in people with Carotid Artery Disease, run by Azienda Ospedaliera Ordine Mauriziano di Torino at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Carotid Artery Disease
- What is being tested?
- Evolocumab and lipid-lowering therapy (LLT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2021to 31 Mar 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- asymptomatic patients with uni- or bilateral carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dL despite ongoing lipid lowering therapy
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera Ordine Mauriziano di Torino
Turin, Piedmont, 10134
Tiziana Claudia Aranzulla, MD, +393383145483, aranzulla.tiziana@gmail.com
Irene Borsotti, +390115082222, lborsotti@mauriziano.it
About this study
Official title: 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
Read the 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.
- Conditions
- Carotid Artery Disease
- Being tested
- Evolocumab, lipid-lowering therapy (LLT)
- Medical subject headings
- Carotid Artery Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha
Evolocumab 140 mg s.c. every two weeks on top of optimal lipid lowering therapy
lipid-lowering therapy (LLT)Other
lipid-lowering therapy (LLT)
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Active comparator | Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy Receives: Drug: Evolocumab; Other: lipid-lowering therapy (LLT) |
| Standard | Placebo comparator | No further treatment besides optimal lipid-lowering therapy will be administered Receives: Other: lipid-lowering therapy (LLT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphological carotid plaque stabilization
Morphological stabilization of the carotid plaque evaluated with Carotid duplex ultra-sonography
Measured: 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.
Measured: 12 months
Secondary outcomes (2)
Changes of LDL-C
Absolute changes of LDL-C
Measured: 12 months
Major adverse cerebrovascular events
All-cause mortality, cardiovascular mortality, stroke, myocardial infarction, any coronary or peripheral revascularization
Measured: 12 and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start1 Mar 2021
- Primary completion31 Mar 2022 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carotid Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized controlled study
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera Ordine Mauriziano di Torino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tiziana Claudia Aranzulla, Azienda Ospedaliera Ordine Mauriziano di Torino
- Investigators
- Tiziana Claudia Aranzulla, MD, Principal investigator, A.O. Ordine Mauriziano di Torino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730973
- Sponsor's protocol ID
- 2020-005663-31
- Acronym
- CARUSO
- Status last verified
- Jul 2021
- First submitted
- 24 Jan 2021
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 33893754Clezar CN, Flumignan CD, Cassola N, Nakano LC, Trevisani VF, Flumignan RL. Pharmacological interventions for asymptomatic carotid stenosis. Cochrane Database Syst Rev. 2023 Aug 4;8(8):CD013573. doi: 10.1002/14651858.CD013573.pub2.
PubMed 37565307
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CARotid plaqUe StabilizatiOn and Regression With Evolocumab: the CARUSO Study
- ClinicalTrials.gov ID
- NCT04730973
- Acronym / sponsor ID
- CARUSO / 2020-005663-31
- Conditions
- Carotid Artery Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Azienda Ospedaliera Ordine Mauriziano di TorinoUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 31 Mar 2022 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 29 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized controlled study
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Active comparator | Drug: Evolocumab, Other: lipid-lowering therapy (LLT)Subcutaneous evolocumab 140 mg will be administered every 2 weeks on top of optimal lipid-lowering therapy |
| Standard | Placebo comparator | Other: lipid-lowering therapy (LLT)No further treatment besides optimal lipid-lowering therapy will be administered |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- asymptomatic patients with uni- or bilateral carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dL despite ongoing lipid lowering therapy
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: RepathaEvolocumab 140 mg s.c. every two weeks on top of optimal lipid lowering therapy | Drug | Evolocumab |
| lipid-lowering therapy (LLT)lipid-lowering therapy (LLT) | Other | Evolocumab, Standard |
Primary outcome
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.
2 secondary outcomes
Changes of LDL-C
Time frame: 12 months
Major adverse cerebrovascular events
Time frame: 12 and 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Results publication: PubMed 33893754Aranzulla 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.
- Derived from this study: PubMed 37565307Clezar CN, Flumignan CD, Cassola N, Nakano LC, Trevisani VF, Flumignan RL. Pharmacological interventions for asymptomatic carotid stenosis. Cochrane Database Syst Rev. 2023 Aug 4;8(8):CD013573. doi: 10.1002/14651858.CD013573.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tiziana Claudia Aranzulla, MD principal investigator
A.O. Ordine Mauriziano di Torino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Evolocumab and lipid-lowering therapy (LLT) in people with Carotid Artery Disease, run by Azienda Ospedaliera Ordine Mauriziano di Torino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tiziana Claudia Aranzulla, MD (+390115085038, taranzulla@mauriziano.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morphological carotid plaque stabilization (time frame: Six months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04730973, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021; AzTrials last refreshed its copy on 30 Oct 2026.