Evaluation of Evolocumab on Coronary Microvascular Dysfunction in Patients with Atherosclerotic Cardiovascular Disease Undergoing Coronary Angiography
- Trial ID
- 2024-519012-14-00
- Protocol
- 38RC19.186
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare **coronary microvascular dysfunction** (CMVD) four weeks after a single administration of **evolocumab** versus no treatment in patients with **atherosclerotic cardiovascular disease** confirmed by noninvasive imaging tests and requiring coronarography. This objective is clinically relevant as it aims to evaluate the potential therapeutic impact of evolocumab, a PCSK9 inhibitor, on improving coronary microvascular function, which is crucial for patients with atherosclerotic cardiovascular disease, a condition associated with significant morbidity and mortality.
Secondary objectives include:
- Comparing the rate of periprocedural myocardial infarction (MI) between the evolocumab and no treatment groups, which is important for assessing the safety and potential cardiovascular benefits of evolocumab during coronary interventions.
- Investigating the correlation between coronary physiology parameters and imaging data, including coronary angiography, ultrasound, scintigraphy, scanner, and cardiac MRI. This objective seeks to enhance the understanding of the relationship between physiological and imaging findings in coronary artery disease, potentially guiding more precise diagnostic and therapeutic strategies.
Participants
The clinical trial involves participants diagnosed with **atherosclerotic cardiovascular disease**, confirmed through noninvasive imaging tests and requiring coronarography. The study population includes both male and female subjects, aged between 40 to 85 years, with a body weight exceeding 50 kilograms. Participants must have an LDL-C level of at least 0.7 g/L, as assessed within the last six months. The trial does not include a vulnerable population. Participants are required to be affiliated with social security and have provided a signed informed consent form. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the effect of a **PCSK9 inhibitor**, specifically **evolocumab**, on coronary microvascular dysfunction in patients with **atherosclerotic cardiovascular disease** who require coronarography. This is a Phase 4, randomized, double-blind, controlled trial. The study aims to compare coronary microvascular dysfunction four weeks after a single administration of evolocumab versus no treatment. The primary endpoint is the index of microcirculatory resistance measured during invasive coronary angiography. Secondary endpoints include troponin I levels post-percutaneous coronary intervention, coronary angiography parameters, and resting ultrasound parameters.
The trial is expected to last until July 2025, with recruitment having started in January 2021. Participants will be involved for a maximum of four weeks, with the study drug administered as a single subcutaneous injection. The inclusion visit will involve screening to ensure participants meet criteria such as age between 40 to 85 years, weight over 50 kilograms, and an LDL-C level of at least 0.7 g/L. Participants must also be indicated for coronarography according to European guidelines and provide informed consent. Follow-up visits will monitor the primary and secondary endpoints, with the end-of-study visit occurring four weeks post-administration.
Participants may be terminated early from the study if they experience adverse effects, withdraw consent, or if the investigator deems it necessary for safety reasons. The trial is not categorized as low intervention, and the investigational product, Repatha 140 mg solution for injection in a pre-filled pen, is not a pediatric formulation. The study is conducted under the authorization of AMGEN EUROPE B.V., with the investigational product having a maximum daily and total dose of 420 mg. The trial's design ensures rigorous assessment of the investigational product's impact on coronary microvascular dysfunction, contributing valuable data to the field of cardiovascular disease management.
Treatment
The clinical trial involves the administration of **Repatha**, a pharmaceutical product containing the active substance **evolocumab**. Repatha is formulated as a **solution for injection** in a pre-filled pen, specifically designed for subcutaneous injection. Each pre-filled pen contains 140 mg of evolocumab. The maximum total dose administered during the trial is 420 mg, delivered as three separate injections of 140 mg each. The administration is conducted as a single treatment session, with the total dosage not exceeding the specified maximum within a 24-hour period. The product is manufactured by Amgen Europe B.V. and is not a pediatric formulation.
In this study, the experimental treatment with Repatha is compared against a control group that does not receive any treatment. The primary objective is to assess the impact of the PCSK9 inhibitor on coronary microvascular dysfunction in patients with atherosclerotic cardiovascular disease. The trial does not include any additional non-experimental treatments such as standard-of-care therapy or placebo. Participant compliance with the dosing schedule is monitored through direct observation during the administration of the injections, ensuring adherence to the protocol.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the impact of the PCSK9 inhibitor, **evolocumab**, on coronary microvascular dysfunction in patients with atherosclerotic cardiovascular disease. The primary endpoint for efficacy evaluation is the Index of Microcirculatory Resistance (IMR), which will be measured during invasive coronary angiography (ICA) and expressed in mmHg.s. This measurement will be conducted 4 weeks after a single administration of evolocumab or without treatment.
Secondary endpoints include the assessment of Troponin I levels post-percutaneous coronary intervention (PCI), as well as various coronary angiography parameters and coronary physiology metrics such as percentage of epicardial stenosis, Fractional Flow Reserve (FFR), Coronary Flow Reserve (CFR), and IMR. Additionally, resting ultrasound parameters will be evaluated to assess systolic and diastolic function and myocardial deformation. These parameters will provide a comprehensive evaluation of the drug's efficacy in improving coronary microvascular function and overall cardiovascular health in the study population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patient, aged 40 to 85
- More than 50 kilograms
- LDL-C level ≥ 0.7 g / L (biological assessment of less than 6 months)
- For which coronarography is indicated according to European guidelines
- Affiliated with social security
- Signed informed consent form
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 needing coronary microcirculation measurement
- NYHA class III or IV, or last known left ventricular ejection fraction < 30%
- Actual use of PCSK9 inhibitior (evolucumab or others)
- Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN at screening
- LDL apheresis within 12 months prior to randomization
- Active infection or others active disease judge by investigator incompatible with the protocole completion
- 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)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 08 Jan 2021 | 66 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Repatha 140 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS INJECTION | 420 | 1 | PRD3037994 |