Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography (MICROPROTECT)

May 18, 2022 updated by: University Hospital, Grenoble

Effect of Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography : a Monocentric, Prospective, Randomized and Open-label Phase II Trial

Proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (anti-PCSK9) significantly reduce the serum LDL-C level, leading to a regression of the coronary epicardial plaque demonstrated by intracoronary ultrasonography (IVUS), as well as cardiovascular events (CV) in patients with atherosclerotic CV disease treated with statin. The impact of PCSK9 inhibition on coronary microcirculation has never been assessed. However, microvascular coronary dysfunction (CMVD) is a powerful prognostic marker, irrespective of conventional CV risk factors, but also of the severity of the epicardial coronary involvement detected during coronary angiography. The investigators hypothesized that anti-PCSK9 would decrease CMVD, measured by the microcirculatory resistance index (MRI) during coronary angioplasty (Percutaneous coronary intervention, PCI) in patients with myocardial ischemia proved in myocardial scintigraphy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Grenoble, France
        • Recruiting
        • Grenoble University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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 Coronary Artery Bypass Graft Surgery (CABG)
  • Prior myocardial infarction in the territory of ischemia
  • New York Heart Association (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 inhibitor (evolocumab 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
  • Creatinine Phosphokinase (CPK) > 5 ULN at screening
  • Active infection or others active disease judge by investigator incompatible with the protocol completion
  • Main known active infection including positive viral serology (Human Immunodeficiency Virus, Hepatitis B Virus and Hepatitis C Virus)
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Evolocumab, 420 milligrams
Single injection of 420 milligrams of evolocumab (REPATHA®) one month before coronary angiography and coronary microcirculation (IMR) measurement.
Drug: Evolocumab 140 MG/ML [Repatha]
3 injections of evolocumab 140 milligrams performed within 30 minutes and self-administered (subcutaneously in the abdomen, thigh, or upper arm)
No Intervention: Control arm
Measurement of coronary microcirculation (IMR) during coronary angiography, without prior evolocumab injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of a PCSK9 inhibitor treatment on coronary microvascular dysfunction (CMVD) at 4 weeks in patients with atherosclerotic cardiovascular disease.
Time Frame: 4 weeks
Index of microcirculatory resistance (IMR), measured during invasive coronary angiography and expressed in mmHg.s
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of a PCSK9 inhibitor treatment on soluble VE-cadherin rate (sVE).
Time Frame: 4 weeks
Measurement of sVE rate at baseline and four weeks after treatment with evolocumab or without treatment.
4 weeks
Impact of a PCSK9 inhibitor treatment on brachial hyperemia (HB).
Time Frame: 4 weeks
Variation of the luminal diameter of the humeral artery with baseline and four weeks after treatment with evolocumab or without treatment.
4 weeks
Impact of a PCSK9 inhibitor treatment on the rate of peri-procedural myocardial infarction.
Time Frame: 4 weeks
Troponin I level after PCI (peri-procedural myocardial pain will be defined as a post-angioplasty troponin level 10 times higher than the 99th percentile of troponin I).
4 weeks
Correlations between invasive and non-invasive (myocardial scintigraphy - myocardial perfusion entropy (MPE), concentration of sVE, HB) measurements of coronary microvascular dysfunction.
Time Frame: 4 weeks
IMR, MPE, sVE and the variation of the luminal diameter of the humeral artery.
4 weeks
Correlations between the cardiovascular risk and the concentration of sVE and MPE.
Time Frame: 4 weeks
Risk score, sVE rate and MPE.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Investigators

  • Principal Investigator: Gilles BARONE-ROCHETTE, MD, PhD, CHU Grenoble Alpes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2021

Primary Completion (Anticipated)

November 1, 2022

Study Completion (Anticipated)

November 1, 2022

Study Registration Dates

First Submitted

April 3, 2020

First Submitted That Met QC Criteria

April 7, 2020

First Posted (Actual)

April 8, 2020

Study Record Updates

Last Update Posted (Actual)

May 19, 2022

Last Update Submitted That Met QC Criteria

May 18, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC19.186

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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