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

NCT ID: NCT06070974

Last Updated: 2023-10-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-03
• Study Completion Date: 2026-04-30

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.

Conditions

STEMI

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Single arm study

STEMI patients, who meet all the inclusion and none of the exclusion criteria, will be enrolled 3 days after PCI to study the correlation between exosome profile and severity of myocardial infarction

CMR and blood collection

Intervention Type: DIAGNOSTIC_TEST

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).

Interventions

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).

Intervention Type: DIAGNOSTIC_TEST

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Auxologico Italiano

OTHER

Sponsor Role: collaborator

Centro Cardiologico Monzino

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Baggiano, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Centro Cardiologico Monzino

Locations

IRCCS Centro Cardiologico Monzino

Milan, Milan, Italy

Site Status: RECRUITING

Istituto Auxologico Italiano

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Andrea Baggiano, MD

Role: CONTACT

andrea.baggiano@cardiologicomonzino.it

0258002139

Marta Zarà, PhD

Role: CONTACT

marta.zara@cardiologicomonzino.it

0258002755

Facility Contacts

Andrea Baggiano, MD

Role: primary

andrea.baggiano@cardiologicomonzino.it

0258002139

Marta Zarà, PhD

Role: backup

marta.zara@cardiologicomonzino.it

0258002755

Silvia Castelletti, MD

Role: primary

s.castelletti@auxologico.it

References

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.

Reference Type: BACKGROUND

PMID: 28856546 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31326993 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 32029601 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34360827 (View on PubMed)

Other Identifiers

CCM 1931

Identifier Type: -

Identifier Source: org_study_id