Clinical trial NCT05727982: Identification of Molecular Mechanisms of Coronary Instability in Homogeneous Subsets of Patients With Acute Coronary Syndromes for the Implementation of Precision Medicine
Official title: Identification of Molecular Mechanisms of Coronary Instability in Homogeneous Subsets of Patients With Acute Coronary Syndromes for the Implementation of Precision Medicine (PRECISION Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Coronary Syndrome
Chronic Coronary Syndrome
Keywords: Atherosclerotic plaque
Optical Coherence Tomography
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-02-14
Enrollment: 400
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 1. Patients with plaque rupture and inflammation;
2. Patients with plaque rupture without inflammation;
3. Patients with intact fibrous plaque with evidence of thrombus (plaque erosion);
4. Patients with a smooth plaque.

Brief summary: To further improve the outcome of ACS it is strongly needed to identify new therapeutic targets. This is possible only by improving our knowledge of the multiple molecular mechanisms leading to coronary instability through several pathways. The goal of this project is to define the molecular mechanisms responsible for the four different presentations of ACS, to identify biomarkers for their noninvasive identification and potential new therapeutic targets, thus promoting precision medicine.

Detailed description: This is a multicenter prospective observational study, involving 5 Research Units (RU), the enrollment-phase will take 18 months (month 6 to 24). This is an explorative project that will prospectively enroll: 1) Consecutive patients with an admission diagnosis of ACS with Non ST elevation myocardial infarction (NSTEMI) confirmed at coronary angiography, undergoing OCT evaluation of the culprit coronary plaque before stent implantation for clinical reasons and with a clearly identifiable feature of the culprit plaques according to current European guidelines. ECG changes may include transient ST- segment elevation, persistent or transient ST-segment depression, T-wave inversion, flat T waves or pseudo- normalization of T waves or the ECG may be normal. Taking into account our previous studies, the investigators estimated that between 30-35% of NSTEMI patients will undergo OCT evaluation; 2) Consecutive patients with symptoms of Stable Angina (SA) lasting \>12 months, angiographically confirmed coronary artery disease, without any episode suggestive of previous acute event, and no overt ischemic episodes during the last 48 hours, according to current European guidelines. Myocardial ischemia was documented by afunctional test (ie, exercise treadmill testing and/or myocardial perfusion imaging). Patients showing Q waves on 12-lead electrocardiogram and/or abnormal echocardiogram (ie, left ventricular ejection fraction \<40% and/or wall motion abnormalities) were excluded. NSTEMI (within 12 hours of symptom onset) and SA patients will be enrolled at the time of their admission to the Coronary Care Unit and to the SubIntensive Cardiac Care Unit, of wich Prof. Giovanna Liuzzo (project PI) is the supervising physician; 3) In the same period, consecutive Mitral Valve Disease patients (MVD) with angiographically normal coronary arteries undergoing surgery for mitral valve regurgitation, age and sex matched 1:3 with NSTEMI patients, will be enrolled as control group. MVD patients will be enrolled at Cardiosurgery Operative Unit, lead by Professor Massimo Massetti.

Our RU1 will enroll:

1. 150 consecutive patients with an admission diagnosis of NSTEMI.
2. 50 consecutive patients with a diagnosis of SA.
3. 50 consecutive MVD.

Eligibility criteria: Inclusion Criteria:

* Men and post-menopause women of age 45-80 years; ability to understand and sign the informed consent;
* For NSTEMI and SA patients inclusion criteria will include evidence of obstructive atherosclerosis (\> 70% stenosis) at invasive coronary angiography;

Exclusion Criteria:

* Evidence of inflammatory or infectious diseases, malignancies, immunological or haematological disorders;
* Ejection fraction less than 40%;
* Treatment with anti-inflammatory drugs other than low-dose aspirin, and with antibiotic therapies until 1 month before the enrollment.

Primary outcomes:
measure: Identify homogeneous subsets of ACS patients at OCT interrogation of the culprit plaque
timeFrame: 2 week
Secondary outcomes:
measure: Assess the role of shear stress in coronary instability
timeFrame: 1 year
measure: Establish the most efficient and cost-effective biomarker panel
timeFrame: 1 years
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli
Study officials:
References: