atherosclerotic cardiovascular disease
Conditions
Interventions
Trade Name: Repatha
Product Name: EVOLOCUMAB
Pharmaceutical Form: Solution for injection in pre-filled pen
Sponsors
University Hospital Grenoble
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female patient, aged 40 to 85, - More than 50 kilograms - Defined at high cardiovascular risk according to European guidelines - LDL-C level = 0.7 g / L (biological assessment of less than 6 months) - Having benefited from myocardial scintigraphy - For which coronarography is indicated according to European guidelines - Affiliated with social security, - Signed informed consent form Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: - Clinical presentation of unstable angina - Patient whose state of physical or psychological health could compromise the obtaining of his informed consent and his compliance with the requirements of the protocol, with the study evaluation, procedures or completion. - End stage disease (estimated survival of less than one year) - Severe renal dysfunction, defined as an estimated creatinine clearance (MDRD) 180 mmHg or diastolic BP (DBP) > 110 mmHg - Actual use of PCSK9 inhibitior (evolucumab or others) - Untreated or inadequately treated hyperthyroidism or hypothyroidism, controlled by biological assessment if needed, defined by thyroid stimulating hormone (TSH) 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at screening - Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN at screening - Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal) - Personal or family history of hereditary muscular disorders - LDL apheresis within 12 months prior to randomization - CPK> 5 ULN at screening - Active infection or others active disease judge by investigator incompatible with the protocole completion - Main known active infection including positive viral serology (HIV, HBV and HCV) - Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years - Known sensitivity to evolocumab or their excipients to be administered during dosing or natural rubber / latex - Patient likely to not be available to complete all protocol-required study visits or procedures. - Patient in exclusion period of another study - Woman able to procreate in the absence of highly effective contraception - Persons referred to in Articles L1121-6 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare coronary microvascular dysfunction (CMVD) 4-week after a single administration with evolocumab or without treatment, in patients with atherosclerotic cardiovascular disease proved by myocardial ischemia and needing coronarography.;Secondary Objective: -To analyse the impact of a PCSK9 inhibitor treatment on soluble VE-cadherin rate (sVE). -To analyse the impact of a PCSK9 inhibitor treatment on brachial hyperemia (HB). -To compare the rate of periprocedural myocardial infarction (MI) in the evolocumab and no treatment groups. -To analyze the correlations between invasive and non-invasive (myocardial scintigraphy - myocardial perfusion entropy (MPE), concentration of sVE, HB) measurements of coronary microvascular dysfunction. -To analyze the correlations between the cardiovascular risk on the one hand, and the concentration of sVE and MPE on the other hand. ;Primary end point(s): Index of microcirculatory resistance (IMR), measured during invasive coronary angiography (ICA) (in mmHg.s).;Timepoint(s) of evaluation of this end point: 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - sVE rate at baseline and four weeks after treatment with evolocumab or without treatment. - Variation of the luminal diameter of the humeral artery with baseline and four weeks after treatment with evolocumab or without treatment. - Troponin I level after PCI. - IMR, MPE, sVE and the variation of the luminal diameter of the humeral artery. - Risk score, sVE rate and MPE.;Timepoint(s) of evaluation of this end point: Baseline, 4 weeks after treatment with evolocumab or without treatment. | — |
Countries
France
Contacts
Public ContactTinaig le Costaouec
University Hospital Grenoble
Outcome results
None listed