The objective of the study will be to analyse the diagnostic and prognostic value of circulating inflammatory and/or coagulation biomarkers in plasma, plasma Extracellular Vesicles (EV), and gene expression profiles of circulating cells for the…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter: plasma EV proteins for obstructive coronary artery
disease in patients presenting with CCS-like symptoms in the cardiology
outpatient department.
Secondary outcome
Secondary study parameters/endpoints are:
• To assess the added value of other plasma EV biomarkers associated with
inflammation and/or coagulation and cardiovascular disease to plasma EV
proteins in detection of CCS.
• To assess prediction of myocardial ischemia and revascularization with plasma
EV proteins and with (addition of) other plasma EV biomarkers associated with
inflammation and/or coagulation.
• To assess identification of high-risk CCS patients with plasma EV proteins
and plasma (EV) biomarkers associated with inflammation and/or coagulation
(plaque burden P3 or P4, or with plaque vulnerability (HRP) according to
CAD-RADS 2.0).
• To compare the diagnostic and prognostic value of plasma EV proteins and
plasma (EV) biomarkers associated with inflammation and/or coagulation with
calcium scoring.
• Comparison with ICA/FFR.
• To compare and assess the prognostic value of plasma EV proteins and plasma
(EV) biomarkers associated with inflammation and/or coagulation during the 30
month follow up: 1) In planned revascularization procedures due to obstructive
CAD; 2) In all-cause mortality; 3) in Major Adverse Cardiac Events (MACE),
which comprises a) Cardiovascular mortality, b) aborted sudden cardiac death,
c) Myocardial Infarction (MI); d) Unplanned hospitalization for chest pain
leading to urgent revascularization; e) Stroke.
Background summary
Coronary artery disease (CAD) is a leading cause of morbidity and mortality in
the Netherlands, like in other Western Countries, and can be divided in Acute
Coronary Syndrome (ACS) and Chronic Coronary Syndrome (CCS). Early diagnosis of
CCS is essential, because of the improvement of the prognosis following timely
interventions. On the contrary, early rule out of CCS reduces costs (e.g.
diagnostic procedures, hospital admissions) and patient burden. Inflammatory
and coagulation protein biomarkers in Extracellular Vesicles have emerged as a
highly potential diagnostic value in the early detection of CCS, as literature
showed that EV protein levels were associated with future cardiovascular risk.
The Myomarker study, which is the predecessor of the CUSTODIAN study,
hypothesized that 5 EV proteins (CD14, Cystatin C, Serpin C1, Serpin G1 and
Serpin F2) could predict chronic coronary syndrome. The results of this study
could only be interpreted as a hypothesis, since it was a retrospective single
centre analysis with a small sample size. Therefore, the CUSTODIAN study is
set-up to address the limitations of the Myomarker study and to further study
the association between the identified EV proteins and CCS via a multi-centre
prospective observational cohort study.
Study objective
The objective of the study will be to analyse the diagnostic and prognostic
value of circulating inflammatory and/or coagulation biomarkers in plasma,
plasma Extracellular Vesicles (EV), and gene expression profiles of circulating
cells for the diagnosis of CCS.
Study design
The study is a prospective and diagnostic cohort study.
Study burden and risks
No risks are associated with participation in this study, as only extra blood
required for the EV isolation will be withdrawn from the intravenous access
device which is already inserted as part of standard care prior to the CCTA
scan. The total amount of venous blood taken is not considered harmful for any
patient. No additional harm is expected to the patient as the insertion of an
intravenous access device is part of standard clinical care. Furthermore, no
direct benefits are expected for the participants.
Padualaan 8
Utrecht 3584 CH
NL
Padualaan 8
Utrecht 3584 CH
NL
Listed location countries
Age
Inclusion criteria
• The subject is >= 18 years of age
• The subject is willing and able to provide informed consent and adhere to
study rules and regulations and follow-up
• The subject has (recurrent) angina pectoris or an equivalent, suspected of
stable coronary artery disease, based on symptoms and signs, history, clinical
examination and baseline diagnostic testing (e.g., ECG recording and laboratory
tests) as described in the 2019 ESC guideline on chronic coronary syndromes.
• The subject will undergo a >=64 multidetector row CCTA (with contrast) as part
of usual care deemed by the treating physician.
Exclusion criteria
• The subject does not or is not able to comply with those imaging guidelines
for the performance and acquisition of CCTA by the Society of Cardiac Computed
Tomography (SCCT)1 established to obtain good image quality, including:
o The subject is morbidly obese (Body Mass Index (BMI) > 40).
o The subject is not able to sustain a breath-hold for 25 seconds.
• The subject is unable to remain in supine position for at least 30 minutes
• The subject is suffering from unstable angina pectoris.
• The subject is suffering from decompensated congestive cardiac failure.
• The subject is suffering from a known or suspected non-ischemic
cardiomyopathy.
• The subject has a history of Percutaneous Coronary Intervention (PCI) or
coronary artery bypass grafting (CABG).
• The subject currently has pacemaker- or internal defibrillator leads
implanted.
• The subject has a prosthetic heart valve.
• The subject is suffering from (auto)immune disorders
• The subject is suffering from an active malignancies and/or currently
receives treatment for a malignancy
• The subject is currently receiving oral, systemic or long-term cutaneous
steroid therapy, or any other oral or systemic immune-suppressive medications.
• The subject is currently receiving therapeutic anticoagulants, such as direct
oral anticoagulants, vitamin K antagonists, heparin or low molecular weight
heparin. Patients taking thrombocyte aggregation inhibitors and prophylactic
anticoagulants are allowed to participate. • The subject is suffering from a
coagulation disorder
• The subject is or might be pregnant.
• The subject participates in any other clinical trial that interferes with the
current study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86527.100.24 |