A Phase 4 interventional study of Coronary angiography and OCT imaging in Myocardial Infarction With Non-Obstructive Coronary Arteries, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Active, not recruiting at 3 sites in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-26.
Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Phase 4, Interventional, and Treatment
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.
PROMISE study is a randomized multicenter prospective superiority phase IV trial comparing "precision medicine approach" versus "standard of care" in improving the prognosis and/or the quality-of-life of patients presenting with MINOCA. Patients will be randomized 1:1 to "precision medicine approach" consisting of a comprehensive diagnostic work up aim at elucidating the pathophysiological mechanism of MINOCA and consequently a tailored pharmacological approach versus "standard of care" consisting of standard diagnostic algorithm and therapy for myocardial infarction.
The aim of the 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 (primary objective). 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 (secondary objectives). 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 (secondary objective).
The study is a multicentre trial involving 3 centers: IRCCS Fondazione Policlinico Universitario A. Gemelli (Study Promoter), Centro Cardiologico Monzino IRCCS, IRCCS Policlinico San Donato.
It will include 180 patients aged >18 years hospitalized for MINOCA randomized 1:1 to a "precision medicine approach" consisting of a comprehensive diagnostic work-up, analysis of circulating biomarkers and micro RNA expression profile and pharmacological treatment specific for the underlying cause versus a "standard approach" consisting of routine diagnostic work-up and standard medical treatment.
29 studies on the registry are indexed under MINOCA; 18 are open to participants now.
Browse MINOCA studies →Fondazione Policlinico Universitario Agostino Gemelli IRCCS is the lead sponsor of 952 studies on the registry; 541 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
MINOCA diagnosis, defined as:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Comprehensive diagnostic work-up with: * Coronary angiography and ventriculography in all patients * OCT at the time of coronary angiography in the cath-lab. * Acetylcholine provocative test (to assess the presence of coronary vasospasm) at the time of coronary angiography in the cath-lab. * TE-Echo and/or CE-Echo (if distal/microvascular embolization is suspected) * Blood sampling for circulating biomarkers and miRNA expression profile * Trans-thoracic echocardiography in all patients during the index hospitalization * CMR in all cases during the index hospitalization. Targeted pharmacological treatment specific for the underlying cause: * DAPT ± stent implantation (if required), statins, beta-blockers, ACEi/ARB (in case of evidence of plaque rupture/erosion) * CCB and/or nitrates (in case of documentation of coronary vasospasm) * Anticoagulation (in case of coronary embolism).
Procedure: Coronary angiography · Diagnostic Test: OCT imaging · Procedure: Percutaneous coronary intervention (PCI): · Diagnostic Test: Acetylcholine provocative test · Diagnostic Test: TT-Echocardiography · Diagnostic Test: TE/contrast echocardiography · Diagnostic Test: Cardiac magnetic resonance · Diagnostic Test: Circulating biomarkers · Drug: Antiplatelet Drug · Drug: Statin · Drug: Beta blocker · Drug: ACEi/ARB · Drug: CCB · Drug: Nitrates · Drug: Anticoagulant
Routine diagnostic work-up with: * Coronary angiography and ventriculography * Transthoracic echocardiography in all patients during the index hospitalization * CMR with contrast media only if clinically indicated (i.e. to exclude myocarditis or takotsubo syndrome) Standard medical treatment with: * DAPT in all patients * Beta-blockers (if indicated by the clinical context, i.e. documentation of left ventricular ejection fraction \<50%, tachycardia). * High intensity statins in all patients * ACEi/ARB (if clinically indicated).
Procedure: Coronary angiography · Diagnostic Test: TT-Echocardiography · Diagnostic Test: Cardiac magnetic resonance · Drug: Antiplatelet Drug · Drug: Statin · Drug: Beta blocker · Drug: ACEi/ARB
coronary angiography will be performed via the transradial or transfemoral approach with the use of a 6F sheath. Coronary angiography will be performed within 90 minutes from hospital admission in patients presenting with persistent ST-segment elevation, and within 48 hours in patients presenting with non-ST-segment elevation. Unfractionated heparin (initial weight-adjusted intravenous bolus of 60 IU/Kg, with repeat boluses to achieve an activated clotting time of 250 to 300 seconds) was administered in all patients. If evidence of plaque rupture
OCT imaging will be performed in the culprit artery in all patients randomized to the "precision medicine approach". A 0.014-inch guidewire will be placed distally in the target vessel and an intracoronary injection of 200 µg of nitroglycerine will be performed. Frequency domain OCT (FD-OCT) images are acquired by a commercially available system (C7 System, LightLab Imaging Inc/ St Jude Medical, Westford, MA) connected to an OCT catheter (C7 Dragonfly; LightLab Imaging Inc/ St Jude Medical, Westford, MA), which was advanced to the culprit lesion. The FD-OCT run will be performed using the integrated automated pullback device at 20 mm/s. During image acquisition, coronary blood flow will be replaced by continuous flushing of contrast media directly from the guiding catheter at a rate of 4 ml/s with a power injector in order to create a virtually blood-free environment.
PCI with stent implantation will be considered in selected cases with evidences of plaque rupture
ACh will be administered in a stepwise manner into the left coronary artery (LCA) (20-200 μg) or into the right coronary artery (RCA) (20-50 μg) over a period of 3 min with a 2-3 min interval between injections. Coronary angiography will be performed 1 min after each injection of these agents and/or when chest pain and/or ischaemic ECG shifts were observed. The decision of testing with provocative test LCA or RCA as first will be left to the discretion of the physicians; both LCA and RCA will be tested if the first test was negative. Angiographic responses during the provocative test will be assessed in multiple orthogonal views in order to detect the most severe narrowing and/or analysed by using computerized quantitative coronary angiography (QCA-CMS, Version 6.0, Medis-Software, Leiden, The Netherlands).
TT-Echo will be used to calculate left and right ventricular and atrial dimensions, left and right ventricular systolic function, transmitral flow Doppler spectra, mitral and tricuspidal valve annulus tissue Doppler spectra, ejection time and stroke volume, inferior vena cava, aorta and pulmonary artery diameters and Doppler spectra, according to the recommendations of the American Society of Echocardiography.
In patients with angiographic evidence or suspicion of distal microembolization, TE-Echo consisting of an echocardiographic probe inserted in to the oesophagus will be used to detect a hidden cardioembolic source (i.e. left atrial thrombus); in patients with suspected left ventricular source of cardioembolism, contrast echocardiography consisting of a 0.3ml solution of SONOVUE will be used.
CMR will be performed during hospital stay on a 1.5-T system equipped with a 32-channel cardiac coil. Patients underwent conventional CMR including cine, T2-weighted, first pass perfusion, and conventional breath-held late gadolinium enhancement (LGE).
Blood sampling for circulating biomarkers and miRNA expression profile at the time or within 12 hours of coronary angiography. Blood sampling will be processed and analysed in the research laboratory of the Department of Cardiovascular Science. Biological aliquots will be preserved at XBiogem Biobank at Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (see section 33).
acetylsalicylic acid (loading dose 250mg intravenously followed by 75mg orally) + P2Y12 receptor inhibitor (i.e. Clopidogrel, 300 or 600mg loading dose orally, followed by 75 mg orally daily).
i.e. atorvastatin; dosages titrated on the patient's clinical characteristics
i.e. bisoprolol; dosages titrated on blood pressure, ECG, heart rate
Drug pages: ACE inhibitors · Angiotensin receptor blockers (ARBs)
i.e. ramipril; dosages titrated on blood pressure, ECG, heart rate
i.e. diltiazem; dosages titrated on blood pressure, ECG, heart rate
i.e. nitroglycerine; dosages titrated on blood pressure, ECG, heart rate
i.e. warfarin; the selection of the anticoagulant agent will be based on the clinical scenario, contraindications etc
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.
Time frame: 1-year follow-up
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.
Time frame: 1-year follow-up
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.
Time frame: 1-year follow-up
Healthcare primary related-costs
Healthcare primary related costs will be evaluated as mean costs (including procedures, tests, medicines).
Time frame: 1-year follow-up
Healthcare secondary related-costs
Healthcare secondary related-costs will be evaluated as mean quality adjusted life year (QALY) gained.
Time frame: 1-year follow-up
Healthcare secondary related-costs
Healthcare secondary related-costs will be evaluated as the incremental cost-effectiveness ratio (ICER) expressed as the cost per QALY.
Time frame: 1-year follow-up
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-ΔΔCT Method).
Time frame: during index hospitalization (at the time or within 12 hours of coronary angiography)
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).
Time frame: during index hospitalization (at the time or within 12 hours of coronary angiography)
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).
Time frame: during index hospitalization (at the time or within 12 hours of coronary angiography)
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).
Time frame: during index hospitalization (at the time or within 12 hours of coronary angiography)
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).
Time frame: from day 3 to day 7 from the acute coronary event
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.
Time frame: from day 3 to day 7 from the acute coronary event
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.
Time frame: from day 3 to day 7 from the acute coronary event
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).
Time frame: from day 3 to day 7 from the acute coronary event
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).
Time frame: from day 3 to day 7 from the acute coronary event
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 %).
Time frame: from day 3 to day 7 from the acute coronary event
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.
Time frame: from day 3 to day 7 from the acute coronary event
PDFs hosted by the registry, ClinicalTrials.gov.
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