Effect of impact of PCSK9 inhibitor on coronary microvascular dysfunction in patients with atherosclerotic cardiovascular disease needing coronarography.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Grenoble Alpes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

15 Sep 2020 → ongoing

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Federation of Cardiology

External identifiers

EU CT number

2024-519012-14-00

EudraCT number

2019-003360-45

ClinicalTrials.gov

NCT04338165

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 noninvasive imaging test and needing coronarography.

Secondary objectives 2

1. To compare the rate of periprocedural myocardial infarction (MI) in the evolocumab and no treatment groups.
2. Correlation between coronary physiology parameters and imaging data (coronary angiography, ultrasound, scintigraphy, scanner and cardiac MRI).

Conditions and MedDRA coding

atherosclerotic cardiovascular disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female patient, aged 40 to 85
2. More than 50 kilograms
3. LDL-C level ≥ 0.7 g / L (biological assessment of less than 6 months)
4. For which coronarography is indicated according to European guidelines
5. Affiliated with social security
6. Signed informed consent form

Exclusion criteria 18

1. Clinical presentation of unstable angina
2. 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.
3. End stage disease (estimated survival of less than one year)
4. Severe renal dysfunction, defined as an estimated creatinine clearance (MDRD) < 30 mL/min at screening
5. 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
6. Contra-indication to heparin: hypersensitivity to active substance or to any of the excipients, past heparin induced thrombopenia type II, haemorrhage.
7. Prior CABG
8. Prior myocardial infarction in the territory needing coronary microcirculation measurement
9. NYHA class III or IV, or last known left ventricular ejection fraction < 30%
10. Actual use of PCSK9 inhibitior (evolucumab or others)
11. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN at screening
12. LDL apheresis within 12 months prior to randomization
13. Active infection or others active disease judge by investigator incompatible with the protocole completion
14. Known sensitivity to evolocumab or their excipients to be administered during dosing or natural rubber / latex
15. Patient likely to not be available to complete all protocol-required study visits or procedures.
16. Patient in exclusion period of another study
17. Woman able to procreate in the absence of highly effective contraception
18. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 3

1. Troponin I level after PCI.
2. Coronary angiography parameters and coronary physiology: % epicardial stenosis, FFR, CFR, IMR
3. Resting ultrasound parameters: systolic and diastolic function, myocardial deformation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Grenoble Alpes

Sponsor organisation

Centre Hospitalier Universitaire Grenoble Alpes

Address

Boulevard De La Chantourne, Cs 10217, La Tronche Cs 10217 La Tronche

City

Grenoble Cedex 9

Postcode

38043

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

BARONE-ROCHETTE Gilles

Public contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

BARONE-ROCHETTE Gilles

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications