Clinical trial NCT03851263: Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion
Official title: Multi-slice CT Scan Assessment of the Impact of PCSK9 Inhibition With Evolocumab on Coronary Perfusion in Patients With Reduced Coronary Fractional Flow Reserve (FFR).
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Lead sponsor: ECRI bv
Sponsor class: INDUSTRY
Collaborators: name: Amgen
name: GE Healthcare
name: HeartFlow, Inc.
First posted: 2019-02-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The MARKOV study is an investigator-sponsored single arm, prospective study to assess the effect of evolocumab on the improvement in coronary flow (FFRCT) after 18 and 36 months of treatment in patients with coronary atherosclerosis.

Detailed description: The MARKOV study is an investigator-initiated, open-label, single arm, international, multicenter, prospective study to assess the effect of evolocumab on the improvement in coronary flow (FFRCT) after 18 and 36 months of treatment in patients with coronary atherosclerosis. The study will be conducted in 5 sites in 3 different countries in Europe. Patients will receive evolocumab for approximately 3 year. The expected duration of the entire study from First Subject First Visit to Last Subject Last Follow-up is 46 months (3 year and 10 months).

Eligibility criteria: Inclusion Criteria:

1. At least 2 coronary vessels suitable for CCTA; vessels fulfilling all requirements below: a. patent main branch b. no previous stent placement
2. At least two of the evaluable vessels with subclinical coronary artery disease as defined non-invasively by CCTA with encroachment of the vessel and either: a. Lesion with visual diameter stenosis (DS) \< 50% or, b. Lesion with visual DS ≥ 50% and FFRCT \> 0.80;
3. No planned coronary revascularization (during the course of the study) at the time of enrollment;
4. Most recent, taken within 30 days prior to informed consent form (ICF) signature, fasting LDL-C ≥ 80 mg/dL (≥ 2.07 mmol/L) and on stable statin therapy for at least 30 days at the time of blood sampling, or statin-intolerant or for whom a statin is contraindicated.
5. Subject signed informed consent form

Exclusion Criteria:

1. History of coronary artery bypass surgery, heart transplantation, surgical or percutaneous valve repair and/or replacement
2. New York Heart Association (NYHA) class III or IV heart failure
3. Last known left ventricular ejection fraction \<30%
4. Active liver disease or hepatic dysfunction, either known or defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN)
5. Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2
6. Active malignancy except for adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm (e.g. successfully treated cervical cancer in situ or non-active prostate cancer) Imaging CCTA-related
7. Absence of baseline CCTA obtained in the context of standard clinical care
8. Baseline CCTA not meeting Core Lab quality standards
9. Any contraindication for repeat CCTA such as known anaphylactic allergy to iodinated contrast

   Concomitant and study medication
10. Any prior or current use of PCSK9 inhibition treatment or any other experimental lipid-related drug Other exclusion criteria
11. LDL or plasma apheresis within 12 months of screening
12. Subject \< 18 years of age
13. Legally incompetent to provide written informed consent;
14. Known pregnancy or breast-feeding at time of screening
15. Female subject of childbearing potential, i.e. who are not surgically sterile or post-menopausal (defined as no menses for 2 years without an alternative cause)
16. Male subject with female partner of childbearing potential who is not using highly effective birth control
17. Currently participating in another trial

Primary outcomes:
measure: Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography(CCTA) (FFRCT) at 18 months from baseline
timeFrame: 18 months of treatment
Secondary outcomes:
measure: Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography (FFRCT) at 36 months from baseline.
timeFrame: 36 months of treatment
measure: Percent change of total atheroma burden (TAB) and changes in plaque composition at 18 and 36 months measured by Hounsfield unit of plaque with positive remodeling (>1.10) assessed by coronary computed tomography.
timeFrame: 18 and 36 months of treatment
measure: Change and percent change after 18 and 36 months from baseline of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein (a), triglycerides, apolipoprotein A1 and B.
timeFrame: 18 and 36 months of treatment
measure: Number of treatment emergent adverse events (TEAEs) and adverse events (AEs) of special interest (i.e. acute kidney injury, pregnancy and lactation)
timeFrame: 36 months of treatment
measure: Incidence of all-cause death and the composite of Cardiovascular death, myocardial infarction, stroke, or coronary revascularization. The composite of Cardiovascular death, Myocardial infarction, or stroke
timeFrame: 36 months of treatment
Other outcomes:
Locations:
Study officials:
affiliation: NHLI Imperial College, London
name: Patrick W Serruys, Prof. dr.
role: STUDY_CHAIR
References: