STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

NCT ID: NCT01969890

Last Updated: 2021-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 532 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2018-05-31

Brief Summary

The purpose of this study is to demonstrate that granulocyte colony-stimulating factor (G-CSF) therapy in addition to state-of-the-art treatment (pharmacological and non pharmacological) is safe and significantly improves clinical outcome in patients with reduced left ventricular ejection fraction (LVEF) (≤45%) after successful reperfusion for large anterior acute myocardial infarction.

Detailed Description

Post infarction heart failure (HF) remains a major cause of morbidity and mortality. In the United States, more than three million patients, and 700.000 in Italy, have cardiac failure and its most common cause is ischemic heart disease. The major goal to improve post infarction LV function would be the stimulation of neovascularization and the enhancement of regeneration of cardiac myocytes within the infarcted area. Recent experimental studies suggest that bone marrow-derived progenitor cells (BMCs) or circulating endothelial progenitor cells (cEPCs) contribute to the regeneration of infarcted myocardium, to enhance neovascularization of ischemic myocardium, to prevent cardiomyocyte apoptosis, to alter scar formation by reducing the development of myocardial fibrosis and, thereby, to improve cardiac function.

G-CSF is a hematopoietic cytokine produced by monocytes, fibroblasts and endothelial cells. G-CSF is known to have multiple functions in normal, steady-state hematopoiesis. It is routinely used to mobilize CD34+ hematopoietic stem cells from the BM into peripheral blood, thus enabling their easier collection compared to BM aspirate procedure. The proven efficacy and safety of G-CSF, both in healthy donors and patients with haematological disease, along with favourable results from studies of CD34+ cell transplantation in patients with MI or ischemia, suggest that G-CSF based BMC transplantation may have an efficacy in patients with MI.

Conditions

Anterior Acute Myocardial Infarction; Left Ventricular Systolic Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

G-CSF administration

Granulocyte Colony-Stimulating Factor (G-CSF) administration - 5 microg/kg subcutaneous every 12 hours for 6 days

Group Type: EXPERIMENTAL

G-CSF administration

Intervention Type: DRUG

Zarzio - 5 microg/kg bis in die for 6 days

standard therapy

Standard therapy

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

G-CSF administration

Zarzio - 5 microg/kg bis in die for 6 days

Intervention Type: DRUG

Other Intervention Names

Zarzio

Eligibility Criteria

Inclusion Criteria

• Patients affected by acute anterior ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) or PCI-rescue with persistent occlusion of coronary artery,
• Time symptom-to-balloon (≥3 h and ≤12h or ≤24 h if symptoms persist),
• Thrombolysis in Myocardial Infarction (TIMI) flow post PCI ≥2,
• Evidence of left ventricular (LV) dysfunction (EF biplane ≤45%) ≤24 h after revascularization,
• Men and women aged ≥18 years and ≤75 years,
• Informed consent must be signed before proceeding with any study procedure.

Exclusion Criteria

• Previous anterior MI,
• Recent MI (within 1 month),
• Known previous LV dysfunction (EF <45%),
• Patients with angiographic evidence of coronary anatomy not suitable for PCI, or needing coronary artery bypass grafting (CABG),
• Valve disease requiring surgical correction,
• History of previous cardiac surgery or PCI on LAD within 6 months,
• Previous or current documented history of leukemia, myeloproliferative or myelodysplastic disorder,
• Previous or current documented history of malignant disease,
• Haemoglobin <10 mg/dl,
• White blood cells (WBC) >25.000 mm3,
• Platelet <50.000 mm3,
• Sepsis,
• Known HIV infection,
• Immune system diseases,
• Interstitial lung disease
• Serious concomitant medical conditions (other than ischemic heart disease),
• Pregnancy and breast feeding,
• Documented alcohol and drug abuse,
• Anticipated poor compliance.
• Current participation in a clinical trial with other investigational products
• Other cell therapy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

A. Manzoni Hospital

OTHER

Sponsor Role: collaborator

Centro Cardiologico Monzino

OTHER

Sponsor Role: collaborator

Heart Care Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Felice Achilli, MD

Role: STUDY_CHAIR

Ospedale Alessandro Manzoni - Lecco

Giulio Pompilio, MD

Role: STUDY_CHAIR

Centro Cardiologico Monzino - Milano

Locations

Ospedali Riuniti - SOD Cardiologia Ospedaliera e UTIC

Ancona, AN, Italy

Ospedale Generale Provinciale CG Mazzoni - Divisione di Cardiologia

Ascoli Piceno, AP, Italy

Ospedale San Donato - UO Cardiologia

Arezzo, AR, Italy

AORN Giuseppe Moscati - UO Cardiologia-UTIC

Avellino, AV, Italy

Humanitas Gavazzeni - UO Cardiologia

Bergamo, BG, Italy

Ospedale Bolognini - Divisione di Cardiologia

Seriate, BG, Italy

Ospedale Maggiore - UO Cardiologia

Bologna, BO, Italy

Ospedale Sant'Elia - Cardiologia-UTIC

Caltanissetta, CL, Italy

Ospedale Moriggia Pelascini - UO Cardiologia

Gravedona, CO, Italy

Ospedale Sant'Anna - UOC Cardiologia

San Fermo della Battaglia, CO, Italy

Ospedale Maggiore - UO Cardiologia e UTIC

Crema, CR, Italy

Istituti Ospitalieri - UO Cardiologia

Cremona, CR, Italy

AOU Careggi - Cardiologia Generale 1

Florence, FI, Italy

IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia

Genova, GE, Italy

Ospedale della Misericordia - UO Cardiologia

Grosseto, GR, Italy

Presidio Ospedaliero - UO Cardiologia

Sanremo, IM, Italy

Ospedale Alessandro Manzoni - SCD Cardiologia

Lecco, LC, Italy

Ospedale Campo Marte - UO Cardiologia

Lucca, LU, Italy

Ospedale di Circolo - UOC Cardiologia - UTIC

Desio, MB, Italy

Ospedale San Gerardo - UO Cardiologia UTIC

Monza, MB, Italy

Ospedale Bassini - UO Cardiologia e UTIC

Cinisello Balsamo, MI, Italy

Ospedale Civile - UTIC - Cardiologia

Legnano, MI, Italy

Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC

Milan, MI, Italy

Ospedale Maggiore Policlinico - Divisione di Cardiologia

Milan, MI, Italy

Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC

Milan, MI, Italy

Ospedale San Paolo - Divisione di Cardiologia

Milan, MI, Italy

Ospedale San Luca - Centro Auxologico - UO Cardiologia

Milan, MI, Italy

Ospedale San Carlo Borromeo - Cardiologia UCC

Milan, MI, Italy

Ospedale L. Sacco - Divisione di Cardiologia

Milan, MI, Italy

Ospedale Niguarda - Cardiologia 1 - Emodinamica

Milan, MI, Italy

Istituto Clinico Humanitas - UO Cardiologia Interventistica e UTIC

Rozzano, MI, Italy

Presidio Ospedaliero Carlo Poma - UO Cardiologia

Mantova, MN, Italy

Ospedale San Francesco - Cardiologia UTIC

Nuoro, NU, Italy

Ospedale Giovanni Paolo II - UTIC Cardiologia

Olbia, OT, Italy

Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia

Piacenza, PC, Italy

Azienda Ospedaliera Padova - Clinica Cardiologica

Padua, PD, Italy

AOU Pisana - UO Malattie Cardiovasc. 1-Cisanello

Pisa, PI, Italy

Fondazione IRCCS Policlinico San Matteo - Card. con UCC-Lab. Ricerca Sperim. Card.

Pavia, PV, Italy

Arcispedale Santa Maria Nuova - UO Degenza Cardiologica

Reggio Emilia, RE, Italy

AO San Giovanni Addolorata - Cardiologia 2

Roma, RM, Italy

Ospedale Infermi - UO Cardiologia

Rimini, RN, Italy

AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC

Salerno, SA, Italy

AOU San Giovanni Battista - SCDU Cardiologia 1

Torino, TO, Italy

AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara

Trieste, TS, Italy

Ospedale Ca' Foncello - UOC Cardiologia

Treviso, TV, Italy

Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia

Busto Arsizio, VA, Italy

Presidio Ospedaliero di Saronno - UOC Cardiologia

Saronno, VA, Italy

Ospedale di Circolo Fondazione Macchi - SSD Unità di Cure Intensive Coronariche

Varese, VA, Italy

Ospedale dell'Angelo - UO Cardiologia

Mestre, VE, Italy

Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica

Viterbo, VT, Italy

AORN Cardarelli - UO SC Cardiologia con UTIC

Napoli, , Italy

AOU Federico II - UTIC

Napoli, , Italy

AO Univ. Maggiore della Carità - Cardiologia 2

Novara, , Italy

Countries

Italy

References

Achilli F, Malafronte C, Cesana F, Maggiolini S, Mauro C, De Ferrari GM, Lenatti L, Tespili M, Pasqualini P, Gentile F, Capogrossi MC, Maggioni A, Maseri A, Pontone G, Colombo GI, Pompilio G; STEM-AMI OUTCOME Trial Investigators. Granulocyte-colony stimulating factor for large anterior ST-elevation myocardial infarction: rationale and design of the prospective randomized phase III STEM-AMI OUTCOME trial. Am Heart J. 2015 Oct;170(4):652-658.e7. doi: 10.1016/j.ahj.2015.07.005. Epub 2015 Jul 12.

Reference Type: BACKGROUND

PMID: 26386788 (View on PubMed)

Achilli F, Pontone G, Bassetti B, Squadroni L, Campodonico J, Corrada E, Facchini C, Mircoli L, Esposito G, Scarpa D, Pidello S, Righetti S, Di Gennaro F, Guglielmo M, Muscogiuri G, Baggiano A, Limido A, Lenatti L, Di Tano G, Malafronte C, Soffici F, Ceseri M, Maggiolini S, Colombo GI, Pompilio G; STEM-AMI OUTCOME CMR Sub-Study Investigators. G-CSF for Extensive STEMI. Circ Res. 2019 Jul 19;125(3):295-306. doi: 10.1161/CIRCRESAHA.118.314617. Epub 2019 May 29.

Reference Type: BACKGROUND

PMID: 31138020 (View on PubMed)

Achilli F, Maggiolini S, Madotto F, Bassetti B, Gentile F, Maggioni AP, Colombo GI, Pompilio G; STEM-AMI OUTCOME Trial Investigators. Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial. Heart. 2024 Oct 28;110(22):1316-1326. doi: 10.1136/heartjnl-2024-323926.

Reference Type: DERIVED

PMID: 39401872 (View on PubMed)

Other Identifiers

G112

Identifier Type: -

Identifier Source: org_study_id