Clinical trial NCT05288361: The DISCOVER INOCA Prospective Multi-center Registry
Official title: Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and No Obstructive Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemia and No Obstructive Coronary Artery Disease
Coronary Microvascular Dysfunction
Coronary Vasospasm
Endothelial Dysfunction
Microvascular Angina
Chest Pain With Normal Coronary Angiography
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2022-03-21
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults referred to the catheterization laboratory for evaluation of suspected ischemic heart disease, and who are deemed to have non-obstructive coronary artery disease based on coronary angiography or non-ischemic fractional flow reserve (FFR) or resting free cycle ratio (RFR).

Brief summary: The overall objective of this multi-center registry is to identify specific phenotypes of INOCA with both an anatomic evaluation (coronary angiography and intravascular imaging) and physiologic assessment with the Abbott Coroventis Coroflow Cardiovascular System, and to determine long-term outcomes.

Detailed description: This is a prospective, multicenter, registry of stable patients with ischemia and no obstructive coronary artery disease (INOCA) evaluated by coronary angiography, intravascular imaging, and physiologic measurements obtained on the Coroventis Coroflow Cardiovascular System.

The Coroventis Coroflow Cardiovascular System and PressureWire™ X Guidewire (Abbott, Abbott Park, IL) are a device combination consisting of a physiology wire with wireless transmitter (Wi-Box), CoroHub Receiver, and CoroFlow Software. The PressureWire™ X guidewire is a hydrophilic-coated wire with pressure and temperature sensors that is capable of measuring physiologic indices including fractional flow reserve (FFR), resting full cycle ratio (RFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). The guidewire wirelessly transmits pressure and temperature data via the Wi-Box to the CoroHub Receiver and CoroFlow Software, which is a software interface designed to display pressure measurements, thermodilution curves, and physiologic indices. This registry will enroll 500 subjects at up to 10 sites in the United States that use the Abbott Coroventis Coroflow Cardiovascular System.

The overall objective of this multi-center registry is to identify specific phenotypes of INOCA with both an anatomic evaluation (coronary angiography and intravascular imaging) and physiologic assessment with the Abbott Coroventis Coroflow Cardiovascular System, and to determine long-term outcomes. Specific goals include:

* Describe the prevalence of the following INOCA phenotypes: coronary microvascular dysfunction (CMD), vasospastic angina, mixed CMD/vasospastic angina, other disorders of coronary physiology, and non-cardiac chest pain;
* Characterize the burden of epicardial coronary artery atherosclerosis and myocardial bridging (MB) by angiography and intracoronary imaging (intravascular ultrasound or optical coherence tomography) in patients with INOCA;
* Characterize the natural history and outcomes of patients with INOCA and determine variables associated with major adverse cardiovascular events

Eligibility criteria: Inclusion Criteria:

* Suspected ischemic heart disease and is referred to undergo clinically indicated invasive coronary angiography
* No obstructive coronary artery disease (CAD) as defined by operator visual assessment with (1) angiographically normal coronary arteries OR (2) non-obstructive CAD with angiographic stenosis \< 50%, or greater than or equal to 50 but \< 70% with FFR greater than or equal to 0.81 or RFR greater than or equal to 0.90
* Willing to comply with specified follow-up evaluations. The participant or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)

Exclusion Criteria:

* Pregnant or nursing
* Any myocardial infarction at index presentation or within 90 days prior to enrollment, defined as any electrocardiogram diagnostic for myocardial infarction OR elevation in serum troponin greater than the upper limit of the site-defined reference range
* Known left ventricular ejection fraction \< 50% or cardiogenic shock requiring pressors or mechanical circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist device, other temporary cardiac support blood pump)
* Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation) or dialysis at the time of screening
* Prior percutaneous coronary intervention
* Planned percutaneous coronary intervention (PCI)
* Prior coronary artery bypass graft surgery
* Prior ST-elevation myocardial infarction
* History of hypertrophic cardiomyopathy
* History of infiltrative heart disease (e.g., cardiac amyloidosis)
* New York Heart Association Class IV congestive heart failure
* Severe mitral regurgitation
* Severe aortic stenosis
* Severe pulmonary hypertension (Mean pulmonary artery pressure greater than or equal to 35mmHg or echocardiographic right ventricular systolic pressure greater than or equal to 60mmHg)
* Known history of unrepaired or repaired congenital heart disease
* Past or pending heart transplant, or on the waiting list for organ transplant
* Known other medical illness or known history of substance abuse that may cause non-compliance with the protocol, or is associated with a life expectancy of less than 1 year
* Current or planned participation in a study of an investigational therapy
* Angiographic stenosis in any major epicardial vessel ≥ 70% by visual estimate
* Angiographic stenosis in any major epicardial vessel greater than or equal to 50% and \< 70% by visual estimate with FFR less than or equal to 0.80 or RFR less than or equal to 0.89

Primary outcomes:
measure: The proportion of subjects with each physiologic phenotypes diagnosed with the Coroflow Cardiovascular System will be reported within 24-48 hours of the procedure.
timeFrame: up to 48 hours after the procedure
measure: The proportion of subjects that experience Major Adverse Cardiovascular Events (MACE)
timeFrame: Up to 5 years
measure: The proportion of subjects that exhibit mild, moderate or severe coronary artery stenosis
timeFrame: At the time of the procedure
measure: Lesion length during the procedure
timeFrame: At the time of the procedure
Secondary outcomes:
measure: The proportion of subjects that experience Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) at any time during the study.
timeFrame: Up to 5 Years
measure: The proportion of subjects that die at any time in the study
timeFrame: Up to 5 years
measure: The proportion of subjects that experience a Myocardial Infarction (MI) at any time during the study.
timeFrame: Up to 5 Years
measure: The proportion of subjects that experience a stroke at any time during the study.
timeFrame: Up to 5 years
measure: The proportion of subjects that require revascularization of their coronary arteries at any time during the study.
timeFrame: Up to 5 years
measure: The proportion of subjects that experience a hospitalization at any time during the study.
timeFrame: Up to 5 years
measure: The proportion of subjects that require repeat coronary angiography at any time during the study.
timeFrame: Up to 5 years
measure: The proportion of subjects with coronary lesions that experience progression to obstructive Coronary Artery Disease (CAD) at any time during the study.
timeFrame: Up to 5 years
measure: Proportion of subjects that experience major bleeding at any time during the study using the Bleeding Academic Research Consortium (BARC) bleeding type
timeFrame: Up to 5 years
measure: Proportion of subjects that experience Major Vascular Complications at any time during the study.
timeFrame: Up to five 5 years
measure: Proportion of subjects that experience a composite of death, stroke, and MI at any time during the study.
timeFrame: Up to 5 years
measure: Change from baseline in proportion of subjects that experience each classification of angina status during the study.
timeFrame: At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
measure: The change in baseline of angina symptoms for each subject. The angina status will be classified at the time of the procedure, at 30 days, 6 months, 12months and then annually up to 5 years.
timeFrame: At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
measure: The change in the quality of life (QOL) from baseline for each subject will be assessed using the QOL EQ-5D-5L questionnaire.
timeFrame: At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
measure: The change in depression status from baseline for each subject assessed by the Patient Health Questionnaire (PHQ)-8 questionnaire.
timeFrame: At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
measure: The change in anxiety status from baseline for each subject. will be assessed by the Generalized Anxiety Disorder (GAD)-7 questionnaire.
timeFrame: At baseline, 30 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
measure: The proportion of subjects that experience a series of procedural outcomes as assessed by the site and adjudicated by the CEC.
timeFrame: Up to 48 hours after the procedure
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Health
state: California
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Brooklyn
country: United States
facility: New York Presbyterian-Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Yale University Medical School
name: Samit Shah, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University Medical School
name: Alexandra Lansky, MD
role: PRINCIPAL_INVESTIGATOR
References: