MedPath

STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

Phase 3
Terminated
Conditions
Anterior Acute Myocardial Infarction
Left Ventricular Systolic Dysfunction
Interventions
Registration Number
NCT01969890
Lead Sponsor
Heart Care Foundation
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
532
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
G-CSF administrationG-CSF administrationGranulocyte Colony-Stimulating Factor (G-CSF) administration - 5 microg/kg subcutaneous every 12 hours for 6 days
Primary Outcome Measures
NameTimeMethod
The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure.two years
Secondary Outcome Measures
NameTimeMethod
- All cause death and cardiovascular eventstwo years

The following Cardiovascular events will be assessed:

* recurrence of MI,

* hospitalization due to heart failure,

* cardiovascular death,

* coronary revascularization,

* fatal and non fatal stroke,

* hospitalization due to any cause,

* cardiovascular hospitalization,

* resuscitation and/or appropriate automated implanted cardioverter defibrillator(AICD) therapy.

Trial Locations

Locations (53)

AORN Cardarelli - UO SC Cardiologia con UTIC

🇮🇹

Napoli, Italy

AOU Federico II - UTIC

🇮🇹

Napoli, Italy

AO Univ. Maggiore della Carità - Cardiologia 2

🇮🇹

Novara, Italy

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

Ospedale Bolognini - Divisione di Cardiologia

🇮🇹

Seriate, BG, Italy

Ospedale Maggiore - UO Cardiologia

🇮🇹

Bologna, BO, Italy

Ospedale Moriggia Pelascini - UO Cardiologia

🇮🇹

Gravedona, CO, Italy

Ospedale Maggiore - UO Cardiologia e UTIC

🇮🇹

Crema, CR, Italy

AOU Careggi - Cardiologia Generale 1

🇮🇹

Firenze, FI, Italy

IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia

🇮🇹

Genova, GE, Italy

Ospedale della Misericordia - UO Cardiologia

🇮🇹

Grosseto, GR, Italy

Ospedale Alessandro Manzoni - SCD Cardiologia

🇮🇹

Lecco, LC, Italy

Ospedale Campo Marte - UO Cardiologia

🇮🇹

Lucca, LU, Italy

Ospedale San Gerardo - UO Cardiologia UTIC

🇮🇹

Monza, MB, 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

AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara

🇮🇹

Trieste, TS, Italy

Istituti Ospitalieri - UO Cardiologia

🇮🇹

Cremona, CR, Italy

Ospedale San Luca - Centro Auxologico - UO Cardiologia

🇮🇹

Milano, MI, Italy

Ospedale Niguarda - Cardiologia 1 - Emodinamica

🇮🇹

Milano, MI, Italy

Ospedale Sant'Elia - Cardiologia-UTIC

🇮🇹

Caltanissetta, CL, Italy

Ospedale Sant'Anna - UOC Cardiologia

🇮🇹

San Fermo della Battaglia, CO, Italy

Humanitas Gavazzeni - UO Cardiologia

🇮🇹

Bergamo, BG, Italy

Presidio Ospedaliero - UO Cardiologia

🇮🇹

Sanremo, IM, Italy

Ospedale di Circolo - UOC Cardiologia - UTIC

🇮🇹

Desio, MB, Italy

Ospedale Maggiore Policlinico - Divisione di Cardiologia

🇮🇹

Milano, MI, Italy

Ospedale Civile - UTIC - Cardiologia

🇮🇹

Legnano, MI, Italy

Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC

🇮🇹

Milano, MI, Italy

Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC

🇮🇹

Milano, MI, Italy

Ospedale Bassini - UO Cardiologia e UTIC

🇮🇹

Cinisello Balsamo, MI, Italy

Ospedale San Paolo - Divisione di Cardiologia

🇮🇹

Milano, MI, Italy

Ospedale L. Sacco - Divisione di Cardiologia

🇮🇹

Milano, MI, Italy

Ospedale San Carlo Borromeo - Cardiologia UCC

🇮🇹

Milano, MI, Italy

Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia

🇮🇹

Piacenza, PC, Italy

Azienda Ospedaliera Padova - Clinica Cardiologica

🇮🇹

Padova, 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

AO San Giovanni Addolorata - Cardiologia 2

🇮🇹

Roma, RM, Italy

Ospedale Infermi - UO Cardiologia

🇮🇹

Rimini, RN, Italy

AOU San Giovanni Battista - SCDU Cardiologia 1

🇮🇹

Torino, TO, Italy

Arcispedale Santa Maria Nuova - UO Degenza Cardiologica

🇮🇹

Reggio Emilia, RE, Italy

AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC

🇮🇹

Salerno, SA, Italy

Ospedale Ca' Foncello - UOC Cardiologia

🇮🇹

Treviso, TV, Italy

Presidio Ospedaliero di Saronno - UOC Cardiologia

🇮🇹

Saronno, VA, Italy

Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia

🇮🇹

Busto Arsizio, VA, Italy

Ospedale dell'Angelo - UO Cardiologia

🇮🇹

Mestre, VE, Italy

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

🇮🇹

Varese, VA, Italy

Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica

🇮🇹

Viterbo, VT, Italy

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