Carotid Artery StenosisPhase 4EVOCAR-1NCT03931161
Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1)
A Phase 4 study testing Evolocumab Auto-Injector [Repatha] in people with Carotid Artery Stenosis, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial summary
This is a phase IV, randomised, placebo-controlled, double-blind, parallel group study to determine the effect of Evolocumab treatment on carotid plaque morphology and composition in asymptomatic patients with >50% carotid artery stenosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carotid Artery Stenosis
- What is being tested?
- Evolocumab Auto-Injector [Repatha]
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Sep 2019to 6 May 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Sufficient English language ability to adequately understand the study
- Able to give informed consent
- Significant carotid artery plaque with 50-70% stenosis on ultrasound or MRI performed prior to screening
- Significant asymptomatic carotid artery plaque with >70% stenosis on ultrasound or MRI performed prior to screening, but carotid endarterectomy or carotid artery stenting has been deemed unsuitable by multidisciplinary team during routine clinical care
- Lipid-rich necrotic core (LRNC) on baseline MRI scan
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- Adequate image quality for MRI analysis.
- LDL-C ≥2.6 mmol/L (100 mg/dL)
- On stable dose of maximally-tolerated lipid-lowering therapy in accordance with UK national clinical guidelines (NICE CG18120) for ≥2 months prior to screening. Acceptable non-statin lipid-lowering medications include ezetimibe or a fibrate.
Who cannot join
- Any medical condition which, in the opinion of the investigators, would present an unacceptable risk to the participant if they were to take part in the trial, or prevent them from following the trial protocol
- Current or previous treatment with a PCSK9 inhibitor
- Eligible for PCSK9 inhibitor treatment under current NICE guidelines
- Contra-indication to or inability to use Evolocumab treatment, including:
- Sensitivity to Evolocumab or any associated excipients
- Unable to tolerate or perform self-administration of Evolocumab by auto-injector
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- Lack of suitable refrigerated storage
- Contra-indication to or inability to tolerate MRI
- Estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m2 prior to MRI scan
- Pregnancy or breast-feeding
- Women of childbearing potential who are unwilling or unable to use a highly effective method of contraception
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0HS
About this study
Official title: Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis
This is a phase IV, randomised, placebo-controlled, double-blind, parallel group study to determine the effect of Evolocumab treatment on carotid plaque morphology and composition in asymptomatic patients with >50% carotid artery stenosis.
Read the detailed description
In this study patients will be randomised in a 1:1 ratio to receive Evolocumab 140 mg every two weeks or matching placebo, to be administered for 12 months. After 12 months of treatment, patients will remain in follow-up for a further 12 months.
High resolution magnetic resonance imaging (MRI) will be used to serially monitor the impact of Evolocumab on carotid plaque morphology and composition in patients with significant carotid stenosis who do not meet clinical criteria for carotid endarterectomy. This approach will reveal if clinically beneficial plaque regression occurs, without requiring the large patient cohorts or long follow-up needed for cardiovascular outcome trials.
Results from this study will establish whether treatment with Evolocumab is likely to be beneficial to patients with asymptomatic carotid stenosis.
- Conditions
- Carotid Artery Stenosis
- Being tested
- Evolocumab Auto-Injector [Repatha], Placebo Auto-Injector
- Keywords
- carotid plaque morphology, carotid plaque composition, evolocumab
- Medical subject headings
- Carotid Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evolocumab Auto-Injector [Repatha]Drug
Also called Repatha
Auto-Injector, 140 mg every two weeks.
Placebo Auto-InjectorDrug
Also called Placebo
Matching Placebo for the active comparator (Evolocumab)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching Placebo. Receives: Drug: Placebo Auto-Injector |
| Evolocumab | Active comparator | Evolocumab Auto-Injector [Repatha] Receives: Drug: Evolocumab Auto-Injector [Repatha] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in lipid-rich necrotic core
Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline
Measured: 12 months
Secondary outcomes (9)
Percentage of LRNC core
Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline
Measured: 12 months
LRNC regression
Percentage of participants achieving LRNC regression at 12 months
Measured: 12 months
LRNC volume
Change in carotid plaque LRNC volume at other time-points, compared to baseline
Measured: 24 months
LRNC percentage
Change in carotid plaque LRNC percentage at other time-points, compared to baseline
Measured: 24 months
Measures of other carotid plaque burden - Volume wall thickness
Absolute and percentage change, compared to baseline, of volume wall thickness
Measured: 24 months
Measures of other carotid plaque burden - Volume wall area
Absolute and percentage change, compared to baseline, volume wall area
Measured: 24 months
Measures of other carotid plaque burden - Calcification
Absolute and percentage change, compared to baseline, of plaque composition (calcification)
Measured: 24 months
Measures of other carotid plaque burden - Fibrous tissue volume
Absolute and percentage change, compared to baseline, of plaque composition (fibrous tissue volume)
Measured: 24 months
Measures of other carotid plaque burden - New intra-plaque haemorrhage
Absolute and percentage change, compared to baseline, of plaque composition (new intra-plaque haemorrhage)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start4 Sep 2019
- Primary completion6 May 2023 (estimated)
- Study completion6 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carotid Artery StenosisStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London
- Responsible party
- Sponsor
- Investigators
- Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03931161
- Sponsor's protocol ID
- EVOCAR-1
- Acronym
- EVOCAR-1
- Status last verified
- Oct 2022
- First submitted
- 15 Apr 2019
- Last updated
- 13 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis
- ClinicalTrials.gov ID
- NCT03931161
- Acronym / sponsor ID
- EVOCAR-1 / EVOCAR-1
- Conditions
- Carotid Artery Stenosis
- Keywords
- carotid plaque morphology, carotid plaque composition, evolocumab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Collaborators
- Imperial College London
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 6 May 2023 (estimated)
- Study completion
- 6 May 2024 (estimated)
- First posted
- 30 Apr 2019 (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.
This is a phase IV, randomised, placebo-controlled, double-blind, parallel group study to determine the effect of Evolocumab treatment on carotid plaque morphology and composition in asymptomatic patients with >50% carotid artery stenosis.
Detailed description
In this study patients will be randomised in a 1:1 ratio to receive Evolocumab 140 mg every two weeks or matching placebo, to be administered for 12 months. After 12 months of treatment, patients will remain in follow-up for a further 12 months.
High resolution magnetic resonance imaging (MRI) will be used to serially monitor the impact of Evolocumab on carotid plaque morphology and composition in patients with significant carotid stenosis who do not meet clinical criteria for carotid endarterectomy. This approach will reveal if clinically beneficial plaque regression occurs, without requiring the large patient cohorts or long follow-up needed for cardiovascular outcome trials.
Results from this study will establish whether treatment with Evolocumab is likely to be beneficial to patients with asymptomatic carotid stenosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Auto-InjectorMatching Placebo. |
| Evolocumab | Active comparator | Drug: Evolocumab Auto-Injector [Repatha]Evolocumab Auto-Injector [Repatha] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥18 years
- Sufficient English language ability to adequately understand the study
- Able to give informed consent
- Significant carotid artery plaque with 50-70% stenosis on ultrasound or MRI performed prior to screening
- Significant asymptomatic carotid artery plaque with >70% stenosis on ultrasound or MRI performed prior to screening, but carotid endarterectomy or carotid artery stenting has been deemed unsuitable by multidisciplinary team during routine clinical care
Key exclusion criteria (11 listed)
- Any medical condition which, in the opinion of the investigators, would present an unacceptable risk to the participant if they were to take part in the trial, or prevent them from following the trial protocol
- Current or previous treatment with a PCSK9 inhibitor
- Eligible for PCSK9 inhibitor treatment under current NICE guidelines
- Contra-indication to or inability to use Evolocumab treatment, including:
- Contra-indication to or inability to tolerate MRI
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 |
|---|---|---|
| Evolocumab Auto-Injector [Repatha]Also: RepathaAuto-Injector, 140 mg every two weeks. | Drug | Evolocumab |
| Placebo Auto-InjectorAlso: PlaceboMatching Placebo for the active comparator (Evolocumab) | Drug | Placebo |
Primary outcome
Change in lipid-rich necrotic core
Time frame: 12 months
Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline
9 secondary outcomes
Percentage of LRNC core
Time frame: 12 months
LRNC regression
Time frame: 12 months
LRNC volume
Time frame: 24 months
LRNC percentage
Time frame: 24 months
Measures of other carotid plaque burden - Volume wall thickness
Time frame: 24 months
Measures of other carotid plaque burden - Volume wall area
Time frame: 24 months
Measures of other carotid plaque burden - Calcification
Time frame: 24 months
Measures of other carotid plaque burden - Fibrous tissue volume
Time frame: 24 months
Measures of other carotid plaque burden - New intra-plaque haemorrhage
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2022.
- 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.
Jaimini Cegla, BSc MSc MBBS MRCP FRCPath PhD principal investigator
Imperial College London
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 Auto-Injector [Repatha] in people with Carotid Artery Stenosis, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
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 9 inclusion and 11 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 13 Oct 2022. 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 United Kingdom. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in lipid-rich necrotic core (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2022.