Myocardial Infarction With Non-Obstructive Coronary Arteries Clinical Trial
— PROMISEOfficial title:
PROgnostic Value of Precision Medicine in Patients With Myocardial Infarction and Non-obStructive Coronary artEries: the PROMISE Trial.
The aim of our study is to evaluate if the use of a precision-medicine approach with a specific therapy tailored on the underlying pathogenic mechanism will improve the quality-of-life in MINOCA patients. The investigators further aim at investigating wherever a precision-medicine approach will improve the prognosis, healthcare related costs, and if that a different profile of plasma biomarkers and microRNAs may serve as diagnostic tools for detecting specific causes of MINOCA and to assess response to therapy. Finally, beyond its pivotal role in differential diagnosis, the investigators hypothesize that cardiac magnetic resonance (CMR) may provide a morphological and functional cardiac characterization as well as help in the prognostic stratification.
| Status | Recruiting |
| Enrollment | 180 |
| Est. completion date | July 2025 |
| Est. primary completion date | July 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Ability to give informed consent to the study - Age > 18y - MINOCA diagnosis, defined as: - Acute myocardial infarction (based on Fourth Universal Definition of Myocardial Infarction Criteria): - Evidence of non-obstructive coronary artery disease on angiography (i.e., no coronary artery stenosis >50%) in any major epicardial vessel. - No specific alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, and myocarditis). Exclusion Criteria: - Inability or limited capacity to give informed consent to the study - Age < 18 y - Pregnant and breast-feeding women or patients considering becoming pregnant during the study period will be excluded. For women of childbearing potential, the use of a highly effective contraceptive measure is required in order to be included in the study. "Highly effective contraceptive" is defined in accordance with the recommendations of the Clinical Trial Facilitation Group as a contraceptive measure with a failure rate of less than 1% per year (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG /2020_09_HMA_CTFG_Contraception_guidance_Version_1.1_updated.pdf). - Alternate diagnosis for the clinical presentation (i.e. non-ischemic causes of myocardial injury such as sepsis, pulmonary embolism, valve disease, hypertrophic cardiomyopathy and myocarditis). Also patients presenting with Takotsubo syndrome will be excluded. - Contraindication to contrast-enhanced CMR, eg, severe renal dysfunction (glomerular filtration rate <30 mL/min), non-CMR-compatible pacemaker or defibrillator. - Contraindication to drugs administrated: e.g a history of hypersensitivity to drugs administrated or its excipients, significant renal and/or hepatic disease. - Patients with comorbidities having an expected survival <1-year will be excluded. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Centro Cardiologico Monzino | Milan | |
| Italy | Fondazione Policlinico Universitario A. Gemelli IRCCS | Rome | |
| Italy | IRCCS Policlinico San Donato | San Donato Milanese |
| Lead Sponsor | Collaborator |
|---|---|
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Centro Cardiologico Monzino, IRCCS Policlinico S. Donato |
Italy,
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* Note: There are 20 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Angina status | Angina status will be evaluated using the single-item "angina stability scale" and the two-item "angina frequence scale" of the Seattle Angina Questionnaire (SAQ).
Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. * To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants. |
1-year follow-up | |
| Primary | eattle Angina Questionnaire (SAQ) | Quality of life will be evaluated using the nine-item scale of "physical limitations scale", the three-item "treatment satisfaction scale" and two-item "disease perception scale" of the Seattle Angina Questionnaire (SAQ).
Scores are calculated by summing items within a dimension and transforming it to a 0-100 scale, where 0 is the worst and 100 the best possible level of health. * To reduce the risk of detection and performance bias, a team of 2 cardiologists blinded to group allocation and belonging to an external cardiology unit will submit and collate the questionnaires from study participants. |
1-year follow-up | |
| Secondary | Rates of major adverse cardiovascular events | Rates of major adverse cardiovascular events (MACE; composite of all-cause mortality; re-hospitalization for myocardial infarction, stroke or heart failure; repeated coronary angiography) will be evaluated at 1-year follow-up in MINOCA patients. | 1-year follow-up | |
| Secondary | Healthcare primary related-costs | Healthcare primary related costs will be evaluated as mean costs (including procedures, tests, medicines). | 1-year follow-up | |
| Secondary | Healthcare secondary related-costs | Healthcare secondary related-costs will be evaluated as mean quality adjusted life year (QALY) gained. | 1-year follow-up | |
| Secondary | Healthcare secondary related-costs | Healthcare secondary related-costs will be evaluated as the incremental cost-effectiveness ratio (ICER) expressed as the cost per QALY. | 1-year follow-up | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers:
-miRNAs (miR-16, miR-26a, miR-145, miR-222, miR-155-5p, miR-483-5p, miR-45): to measure miRNA reverse transcriptase polymerase chain reaction (RT-PCR) will be employed and results will be expressed in relative expression (2-??CT Method). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers:
-Endothelin 1: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers:
-Neuropeptide Y: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of different circulating biomarkers as diagnostic biomarker and stratification tool for specific causes of MINOCA. | Measurement of cardiac circulating biomarkers:
-soluble CD40 ligand: It will be assessed through ELISA immunoassay and results will be expressed in Picograms per millilitre (pg/mL). |
during index hospitalization (at the time or within 12 hours of coronary angiography) | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of left and right ventricle volumes (in ml or ml/m2). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of myocardial edema using T2-weighted sequences and a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of defect of perfusion using first pass perfusion sequences and a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of fibrosis using late gadolinium enhancement sequences and a 17 segments assessment model of cardiac segmentation (estimated as LGE % of the cardiac segment involved). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Morphological cardiac characterization will be assessed by measurement of the presence of myocardial infarct size (estimated as grams or % of left ventricular myocardial mass). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Functional cardiac characterization will be assessed by measurement of right and left ventricles eject fraction (estimated as %). | from day 3 to day 7 from the acute coronary event | |
| Secondary | Ability of CMR in evaluating different mechanisms of MINOCA and their prognostic value through morphological and functional cardiac characterization. | Functional cardiac characterization will be assesaed by measurement of regional kinetic abnormalities using a 17 segments assessment model of cardiac segmentation. | from day 3 to day 7 from the acute coronary event |
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