Coronary Artery DiseasePhase 4MARKOVNCT03851263
Multislice Computed Tomography Assessment of PCSK9 Inhibition on Coronary Perfusion
A Phase 4 study testing Evolocumab in people with Coronary Artery Disease, run by ECRI bv.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Aug 2019to 24 Feb 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
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).
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.
Read the 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).
- Conditions
- Coronary Artery Disease
- Being tested
- Evolocumab
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
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).
| Study group | Role | What they receive |
|---|---|---|
| Evolocumab | Experimental | All subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153). Receives: Biological: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in normalized area under the curve of fractional flow reserve derived from coronary computed tomography(CCTA) (FFRCT) at 18 months from baseline
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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
Measured: 36 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2019
- Study start30 Aug 2019 (estimated)
- Primary completion27 Aug 2021 (estimated)
- Study completion24 Feb 2023 (estimated)
Why it stopped: Admisnitrative issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- ECRI bv
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen, GE Healthcare, HeartFlow, Inc.
- Responsible party
- Sponsor
- Investigators
- Patrick W Serruys, Prof. dr., Study chair, NHLI Imperial College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03851263
- Sponsor's protocol ID
- ECRI-11
- Acronym
- MARKOV
- Status last verified
- Dec 2019
- First submitted
- 12 Feb 2019
- Last updated
- 6 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT03851263
- Acronym / sponsor ID
- MARKOV / ECRI-11
- Conditions
- Coronary Artery Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Admisnitrative issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ECRI bvIndustry (pharma, biotech, devices)
- Collaborators
- Amgen, GE Healthcare, HeartFlow, Inc.
- Study start
- 30 Aug 2019 (estimated)
- Primary completion
- 27 Aug 2021 (estimated)
- Study completion
- 24 Feb 2023 (estimated)
- First posted
- 22 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evolocumab | Experimental | Biological: EvolocumabAll subjects are treated with evolocumab 140mg every 2 weeks (q2w) starting on day 1 and ending on day 1071 (week 153). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabSubcutaneous 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). | Biological | Evolocumab |
Primary outcome
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
5 secondary outcomes
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
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
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
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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick W Serruys, Prof. dr. study chair
NHLI Imperial College, London
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Evolocumab in people with Coronary Artery Disease, run by ECRI bv.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 18 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2019.