Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion

NCT03851263 | Withdrawn Phase 4 DMC

• 1 other identifier: ECRI-11
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography(CCTA) (FFRCT) at 18 months from baseline

  18 months of treatment

Secondary Outcomes (5)

• Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography (FFRCT) at 36 months from baseline.

  36 months of treatment

• 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.

  18 and 36 months of treatment

• 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.

  18 and 36 months of treatment

• Number of treatment emergent adverse events (TEAEs) and adverse events (AEs) of special interest (i.e. acute kidney injury, pregnancy and lactation)

  36 months of treatment

• 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

  36 months of treatment

Study Arms (1)

Evolocumab

EXPERIMENTAL

All subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153).

Biological: Evolocumab

Interventions

Evolocumab BIOLOGICAL

Subcutaneous injection, using a pre-filled auto-injector pen. Each pen contains 1.0 ml fluid (containing 140 mg evolocumab) which is injected in the abdomen, thigh or outer area of upper arm every 2 weeks (q2w).

Evolocumab

Eligibility Criteria

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

You may qualify if:

• At least 2 coronary vessels suitable for CCTA; vessels fulfilling all requirements below: a. patent main branch b. no previous stent placement
• 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;
• No planned coronary revascularization (during the course of the study) at the time of enrollment;
• 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.
• Subject signed informed consent form

You may not qualify if:

• History of coronary artery bypass surgery, heart transplantation, surgical or percutaneous valve repair and/or replacement
• New York Heart Association (NYHA) class III or IV heart failure
• Last known left ventricular ejection fraction \<30%
• 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)
• Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2
• 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
• Absence of baseline CCTA obtained in the context of standard clinical care
• Baseline CCTA not meeting Core Lab quality standards
• Any contraindication for repeat CCTA such as known anaphylactic allergy to iodinated contrast
• Concomitant and study medication
• LDL or plasma apheresis within 12 months of screening
• Subject \< 18 years of age
• Legally incompetent to provide written informed consent;
• Known pregnancy or breast-feeding at time of screening
• 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)

Sponsors & Collaborators

• ECRI bv: lead
• Amgen: collaborator
• GE Healthcare: collaborator
• HeartFlow, Inc.: collaborator

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Patrick W Serruys, Prof. dr.

  NHLI Imperial College, London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 22, 2019
• Study Start: August 30, 2019
• Primary Completion: August 27, 2021
• Study Completion: February 24, 2023
• Last Updated: December 6, 2019

Record last verified: 2019-12