Clinical trial NCT06070974: ExosoMe as Integrative Tool for pRognostic Stratification of Adverse Cardiac remodeLing in stEmi Patients: the MIRACLE Study
Official title: ExosoMe as Integrative Tool for pRognostic Stratification of Adverse Cardiac remodeLing in stEmi Patients: the MIRACLE Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: STEMI
Keywords: Cardiovascular Magnetic Resonance
PCI
Exosome
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
Collaborators: name: Istituto Auxologico Italiano
First posted: 2023-10-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive patients with acute STEMI will be screened for study eligibility by site personnel to identify those who meet all selection criteria

Brief summary: This is a multicenter observational prospective study aimed to assess whether plasma exosomes can help identify, at an early stage, patients at high risk of adverse remodeling after STEMI (ST-elevation myocardial infarction) , thus accelerating proper patient management in order to reduce the risk of future cardiovascular events. In order to study the correlation between exosome profile and severity of myocardial infarction, consecutive STEMI patients will be enrolled 3 days after Percutaneous Coronary Intervention (PCI).

Detailed description: Adverse cardiac remodeling is a process of structural and functional changes associated with worse clinical outcomes and increased mortality, which occurs in response to sustained pathophysiological stimuli, such as ST-elevation myocardial infarction (STEMI). Despite the progresses achieved with reperfusion therapy in STEMI, a significant portion of patients still develops adverse remodeling. Cardiovascular Magnetic Resonance (CMR) is the gold standard for clinical diagnosis of adverse remodeling, as it provides reliable and reproducible information on ventricular size, function and tissue damage. However, CMR is not always applicable, due to resources and availability reasons and to patients' contraindications. Therefore, additional markers for the early detection of patients at risk for adverse remodeling after STEMI are needed. Exosomes are small extracellular vesicles released by cells and detectable in all body fluids, including plasma. Their release and cargo are influenced by cellular microenvironment, thus mirroring cell/organ status. Previous study demonstrated that concentration and cargo of plasma exosomes released during STEMI well reflect the pathophysiology of the disease, suggesting their potential as biomarkers. Whether exosome profile analysis could predict adverse remodeling after STEMI remains to be investigated.

The relevant hypothesis to be tested is whether plasma exosomes may help to identify, in an early phase, patients at high risk of adverse remodeling after STEMI, accelerating proper patient management in order to reduce risk of further cardiovascular events and improve outcomes. Overall, this new knowledge will pave the way toward a new strategy to predict adverse remodeling in STEMI patients and to develop patient-tailored therapy.

Eligibility criteria: Inclusion Criteria:

* chest pain suggestive of myocardial ischemia lasting \>30 min
* electrocardiogram (ECG) showing ST-segment elevation \>0.1 mV in more or equal to 2 limb leads or \>0.2 mV in more or equal to 2 contiguous precordial leads, or presumed new left bundle-branch block
* successful treatment with pPCI within 12 h from the onset of symptoms

Exclusion Criteria:

* previous myocardial infarction (MI)
* time to pPCI \>12 h
* atrial fibrillation
* renal failure with glomerular filtration \<30 ml/min
* claustrophobia
* other contraindications to CMR.

Primary outcomes:
measure: Verify whether the profile of circulating plasma exosomes reflects CMR-assessed STEMI severity at hospital discharge
timeFrame: within 3-5 days post PCI
measure: Evaluate whether exosome profile in the acute phase of hospitalization after STEMI predicts adverse remodeling at six months
timeFrame: 6 months
measure: Assess whether changes in exosomes profile a different time points following STEMI (1-3-6 months) reflects clinical outcome
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Monzino
state: Milan
city: Milano
country: Italy
facility: Istituto Auxologico Italiano
Study officials:
affiliation: IRCCS Centro Cardiologico Monzino
name: Andrea Baggiano, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977. doi: 10.1126/science.aau6977.
citation: Zara M, Campodonico J, Cosentino N, Biondi ML, Amadio P, Milanesi G, Assanelli E, Cerri S, Biggiogera M, Sandrini L, Tedesco CC, Veglia F, Trabattoni D, Blandini F, Tremoli E, Marenzi G, Barbieri SS. Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest. Int J Mol Sci. 2021 Jul 28;22(15):8065. doi: 10.3390/ijms22158065.