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

NCT04338165 | Unknown Phase 2 DMC

• 1 other identifier: 38RC19.186
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

Proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody (Anti-PCSK9); Microvascular coronary dysfunction (CMVD); Coronary angioplasty; Cardiovascular imaging

Outcome Measures

Primary Outcomes (1)

• Impact of a PCSK9 inhibitor treatment on coronary microvascular dysfunction (CMVD) at 4 weeks in patients with atherosclerotic cardiovascular disease.

  Index of microcirculatory resistance (IMR), measured during invasive coronary angiography and expressed in mmHg.s

  4 weeks

Secondary Outcomes (5)

• Impact of a PCSK9 inhibitor treatment on soluble VE-cadherin rate (sVE).

  4 weeks

• Impact of a PCSK9 inhibitor treatment on brachial hyperemia (HB).

  4 weeks

• Impact of a PCSK9 inhibitor treatment on the rate of peri-procedural myocardial infarction.

  4 weeks

• Correlations between invasive and non-invasive (myocardial scintigraphy - myocardial perfusion entropy (MPE), concentration of sVE, HB) measurements of coronary microvascular dysfunction.

  4 weeks

• Correlations between the cardiovascular risk and the concentration of sVE and MPE.

  4 weeks

Study Arms (2)

Evolocumab, 420 milligrams

EXPERIMENTAL

Single injection of 420 milligrams of evolocumab (REPATHA®) one month before coronary angiography and coronary microcirculation (IMR) measurement.

Drug: Evolocumab 140 MG/ML [Repatha]

Control arm

NO INTERVENTION

Measurement of coronary microcirculation (IMR) during coronary angiography, without prior evolocumab injection.

Interventions

Evolocumab 140 MG/ML [Repatha] DRUG

3 injections of evolocumab 140 milligrams performed within 30 minutes and self-administered (subcutaneously in the abdomen, thigh, or upper arm)

Evolocumab, 420 milligrams

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

Grenoble University Hospital

Grenoble, France

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Atherosclerosis

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Gilles Barone-Rochette, MD, PhD

  CHU Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gilles Barone-Rochette, MD, PhD

CONTACT

+33476765172; gbarone@chu-grenoble.fr

Clémence Charlon

CONTACT

ccharlon@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 8, 2020
• Study Start: January 8, 2021
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)