ExosoMe as Integrative Tool for pRognostic Stratification of Adverse Cardiac remodeLing in stEmi Patients: the MIRACLE Study

STEMI Clinical Trial

— MIRACLE  

Official title:

ExosoMe as Integrative Tool for pRognostic Stratification of Adverse Cardiac remodeLing in stEmi Patients: the MIRACLE Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06070974
• Other study ID #: CCM 1931
• Status: Recruiting
• Start date: May 3, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: October 2023
• Source: Centro Cardiologico Monzino
• Contact: Andrea Baggiano, MD
• Phone: 0258002139
• Email: andrea.baggiano[@]cardiologicomonzino.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ST Elevation Myocardial Infarction
• STEMI

Intervention

Diagnostic Test:
• CMR and blood collection
All patients enrolled will undergo 2 CMR examination (within 3-5 days post PCI and after six months), and blood collection at third day after PCI (T0). Patients recruited at Centro Cardiologico Monzino will be subjected to a blood withdrawal also at different time points: 1- 3- 6 months after STEMI (T1, T2, and T3 respectively).

Locations

Country	Name	City	State
Italy	IRCCS Centro Cardiologico Monzino	Milano	Milan
Italy	Istituto Auxologico Italiano	Milano

Sponsors (2)

Lead Sponsor	Collaborator
Centro Cardiologico Monzino	Istituto Auxologico Italiano

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977. doi: 10.1126/science.aau6977. — View Citation

Masci PG, Pavon AG, Pontone G, Symons R, Lorenzoni V, Francone M, Zalewski J, Barison A, Guglielmo M, Aquaro GD, Galea N, Muscogiuri G, Muller O, Carbone I, Baggiano A, Iglesias JF, Nessler J, Andreini D, Camici PG, Claus P, de Luca L, Agati L, Janssens S, Schwitter J, Bogaert J. Early or deferred cardiovascular magnetic resonance after ST-segment-elevation myocardial infarction for effective risk stratification. Eur Heart J Cardiovasc Imaging. 2020 Jun 1;21(6):632-639. doi: 10.1093/ehjci/jez179. — View Citation

Pontone G, Carita P, Rabbat MG, Guglielmo M, Baggiano A, Muscogiuri G, Guaricci AI. Role of Cardiac Magnetic Resonance Imaging in Myocardial Infarction. Curr Cardiol Rep. 2017 Aug 31;19(10):101. doi: 10.1007/s11886-017-0907-1. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Verify whether the profile of circulating plasma exosomes reflects CMR-assessed STEMI severity at hospital discharge	Assess the ability of exosome profile, detected in the blood sample 3 days after PCI (T0),to reflect STEMI severity as assessed by CMR and evaluate the correlation of T0 exosome profile with clinicopathological features.	within 3-5 days post PCI
Primary	Evaluate whether exosome profile in the acute phase of hospitalization after STEMI predicts adverse remodeling at six months	Assess the ability of T0 exosomes to predict adverse cardiac remodeling, both alone or in combination with CMR analysis and discover new exosome candidates able to predict adverse cardiac remodeling	6 months
Primary	Assess whether changes in exosomes profile a different time points following STEMI (1-3-6 months) reflects clinical outcome	Evaluate the change of exosomes profile during time and test the correlation of exosomes change during time or at specific time points with clinical complication and outcome	6 months