Carotid stenosis
Conditions
Interventions
Trade Name: Repatha
Product Name: Repatha
Pharmaceutical Form: Injection
INN or Proposed INN: EVOLOCUMAB
CAS Number: 1256937-27-5
Sponsors
Imperial College NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 • Adequate image quality for MRI analysis. • LDL-C =1.8 mmol/L (70 mg/dL) • On stable dose of maximally-tolerated lipid-lowering therapy in accordance with UK national clinical guidelines (NICE CG181) for =2 months prior to screening. Acceptable non-statin lipid-lowering medications include ezetimibe or a fibrate. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: • Any medical condition which, in the opinion of the investigators, would present an unacceptable risk to the patient 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 IMP by auto-injector 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In people who have partial blockage of the major vessels in the neck, which can be linked to stroke, does treatment with Evolocumab change the size and composition of that blockage, as determined by MRI scanning?; Secondary Objective: We will monitor effects of Evolocumab on blood tests parameters such as cholesterol, and also record if participants suffer strokes, heart attacks, or related conditions during the study. We will also assess change in size and composition of the partial blockage of the major neck vessels as determined by ultrasound. ;Primary end point(s): • Change in lipid-rich necrotic core (LRNC) size at 12 months, compared to baseline;Timepoint(s) of evaluation of this end point: 12 months vs baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 months; Secondary end point(s): MRI • Change in percentage lipid-rich necrotic core (LRNC) at 12 months, compared to baseline • Percentage of participants achieving LRNC regression at 12 months • Change in carotid plaque LRNC volume and percentage at other time-points, compared to baseline • Absolute and percentage change in other measures of carotid plaque burden, compared to baseline including: o Volume wall thickness o Volume wall area o Plaque composition (including calcification, fibrous tissue volume and new intra-plaque haemorrhage) US • Change in atheroma burden at 52 weeks, compared to baseline including: o Percentage stenosis o Intimal thickening o Presence of plaque and o Plaque morphology. | — |
Countries
United Kingdom
Contacts
Public ContactCegla
ICHNT
Outcome results
None listed