Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion (MARKOV)
Primary Purpose
Coronary Artery Disease
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Evolocumab
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Any prior or current use of PCSK9 inhibition treatment or any other experimental lipid-related drug Other exclusion criteria
- 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)
- Male subject with female partner of childbearing potential who is not using highly effective birth control
- Currently participating in another trial
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Evolocumab
Arm Description
All subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153).
Outcomes
Primary Outcome Measures
Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography(CCTA) (FFRCT) at 18 months from baseline
Secondary Outcome Measures
Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography (FFRCT) at 36 months from baseline.
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.
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.
Number of treatment emergent adverse events (TEAEs) and adverse events (AEs) of special interest (i.e. acute kidney injury, pregnancy and lactation)
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
Full Information
NCT ID
NCT03851263
First Posted
February 12, 2019
Last Updated
December 4, 2019
Sponsor
ECRI bv
Collaborators
Amgen, GE Healthcare, HeartFlow, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03851263
Brief Title
Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion
Acronym
MARKOV
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
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Admisnitrative issues
Study Start Date
August 30, 2019 (Anticipated)
Primary Completion Date
August 27, 2021 (Anticipated)
Study Completion Date
February 24, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ECRI bv
Collaborators
Amgen, GE Healthcare, HeartFlow, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Evolocumab
Arm Type
Experimental
Arm Description
All subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153).
Intervention Type
Biological
Intervention Name(s)
Evolocumab
Intervention Description
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).
Primary Outcome Measure Information:
Title
Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography(CCTA) (FFRCT) at 18 months from baseline
Time Frame
18 months of treatment
Secondary Outcome Measure Information:
Title
Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography (FFRCT) at 36 months from baseline.
Time Frame
36 months of treatment
Title
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.
Time Frame
18 and 36 months of treatment
Title
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.
Time Frame
18 and 36 months of treatment
Title
Number of treatment emergent adverse events (TEAEs) and adverse events (AEs) of special interest (i.e. acute kidney injury, pregnancy and lactation)
Time Frame
36 months of treatment
Title
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
Time Frame
36 months of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Any prior or current use of PCSK9 inhibition treatment or any other experimental lipid-related drug Other exclusion criteria
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)
Male subject with female partner of childbearing potential who is not using highly effective birth control
Currently participating in another trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick W Serruys, Prof. dr.
Organizational Affiliation
NHLI Imperial College, London
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion
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