- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03851263
Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion (MARKOV)
December 4, 2019 updated by: ECRI bv
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).
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.
Study Overview
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).
Study Type
Interventional
Phase
- Phase 4
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Evolocumab
All subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153).
|
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
18 months of treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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.
Time Frame: 18 and 36 months of treatment
|
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.
Time Frame: 18 and 36 months of treatment
|
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)
Time Frame: 36 months of treatment
|
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
Time Frame: 36 months of treatment
|
36 months of treatment
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Patrick W Serruys, Prof. dr., NHLI Imperial College, London
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
August 30, 2019
Primary Completion (Anticipated)
August 27, 2021
Study Completion (Anticipated)
February 24, 2023
Study Registration Dates
First Submitted
February 12, 2019
First Submitted That Met QC Criteria
February 20, 2019
First Posted (Actual)
February 22, 2019
Study Record Updates
Last Update Posted (Actual)
December 6, 2019
Last Update Submitted That Met QC Criteria
December 4, 2019
Last Verified
December 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Coronary Disease
- Coronary Artery Disease
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Evolocumab
Other Study ID Numbers
- ECRI-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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