Prognostic Value of Precision Medicine in Patients With MINOCA (PROMISE Trial).

Institute of Hospitalization and Scientific Care (IRCCS)

Status and phase: Active, not recruiting; Phase 4

Conditions: Myocardial Infarction With Non-Obstructive Coronary Arteries

Treatments: Diagnostic Test: Acetylcholine provocative test; Drug: CCB; Diagnostic Test: TE/contrast echocardiography; Procedure: Coronary angiography; Diagnostic Test: Cardiac magnetic resonance; Drug: Beta blocker; Drug: Nitrates; Procedure: Percutaneous coronary intervention (PCI):; Drug: Statin; Drug: Antiplatelet Drug; Diagnostic Test: TT-Echocardiography; Diagnostic Test: Circulating biomarkers; Diagnostic Test: OCT imaging; Drug: ACEi/ARB; Drug: Anticoagulant

Study type: Interventional

Funder types: Other

Identifiers

NCT05122780

GR-2019-12370197

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

"Precision medicine approach"

Active Comparator group

Description:

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).

Treatment:

Drug: Anticoagulant

Drug: ACEi/ARB

Diagnostic Test: OCT imaging

Diagnostic Test: Circulating biomarkers

Diagnostic Test: TT-Echocardiography

Drug: Antiplatelet Drug

Drug: Statin

Procedure: Percutaneous coronary intervention (PCI):

Drug: Nitrates

Drug: Beta blocker

Diagnostic Test: Cardiac magnetic resonance

Procedure: Coronary angiography

Diagnostic Test: TE/contrast echocardiography

Drug: CCB

Diagnostic Test: Acetylcholine provocative test

"Standard approach"

Other group

Description:

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).

Treatment:

Drug: ACEi/ARB

Diagnostic Test: TT-Echocardiography

Drug: Antiplatelet Drug

Drug: Statin

Drug: Beta blocker

Diagnostic Test: Cardiac magnetic resonance

Procedure: Coronary angiography