Effect of impact of PCSK9 inhibitor on coronary microvascular dysfunction in patients with atherosclerotic cardiovascular disease proved by myocardial ischemia and needing coronarography.

Phase 1

• Conditions: atherosclerotic cardiovascular disease; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2019-003360-45-FR
• Lead Sponsor: niversity Hospital Grenoble

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-04
• Last Update Posted: 18 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 66

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

-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) < 30 mL/min at screening
-Contra-indication to adenosin : hypersensitivity to active active substance or to any of the excipients, type II or III atrioventricular block or atrial disease (except for pacemaker users), long QT syndrome, severe arterial hypotension, acute heart failure, asthma and severe chronic obstructive pulmonary disease, unstable angina unstabilized by drug therapy, taking dipyridamole, aminophylline, theophylline or other xanthine base within 24 hours prior to adenosine administration
-Contra-indication to heparin: hypersensitivity to active substance or to any of the excipients, past heparin induced thrombopenia type II, haemorrhage.
-Prior CABG
-Prior myocardial infarction in the territory of ischemia
-NYHA class III or IV, or last known left ventricular ejection fraction < 30%
-Known hemorrhagic stroke at any time
-Uncontrolled or recurrent ventricular tachycardia
-Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 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) < lower limit of normal (LLN) or > 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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified