Clinical trial NCT01969890: STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial
Official title: Phase III Study on STem cElls Mobilization in Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Anterior Acute Myocardial Infarction
Left Ventricular Systolic Dysfunction
Lead sponsor: Heart Care Foundation
Sponsor class: OTHER
Collaborators: name: A. Manzoni Hospital
name: Centro Cardiologico Monzino
First posted: 2013-10-25
Enrollment: 532
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure.
timeFrame: two years
Secondary outcomes:
measure: - All cause death and cardiovascular events
timeFrame: two years
Other outcomes:
measure: Safety endpoints - Incidence and severity of bleeding complications, - incidence of malignancy, - incidence and intensity of serious adverse events (SAEs) and adverse drug reactions (ADRs)
timeFrame: two years
Locations:
city: Ancona
country: Italy
facility: Ospedali Riuniti - SOD Cardiologia Ospedaliera e UTIC
state: AN
city: Ascoli Piceno
country: Italy
facility: Ospedale Generale Provinciale CG Mazzoni - Divisione di Cardiologia
state: AP
city: Arezzo
country: Italy
facility: Ospedale San Donato - UO Cardiologia
state: AR
city: Avellino
country: Italy
facility: AORN Giuseppe Moscati - UO Cardiologia-UTIC
state: AV
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni - UO Cardiologia
state: BG
city: Seriate
country: Italy
facility: Ospedale Bolognini - Divisione di Cardiologia
state: BG
city: Bologna
country: Italy
facility: Ospedale Maggiore - UO Cardiologia
state: BO
city: Caltanissetta
country: Italy
facility: Ospedale Sant'Elia - Cardiologia-UTIC
state: CL
city: Gravedona
country: Italy
facility: Ospedale Moriggia Pelascini - UO Cardiologia
state: CO
city: San Fermo della Battaglia
country: Italy
facility: Ospedale Sant'Anna - UOC Cardiologia
state: CO
city: Crema
country: Italy
facility: Ospedale Maggiore - UO Cardiologia e UTIC
state: CR
city: Cremona
country: Italy
facility: Istituti Ospitalieri - UO Cardiologia
state: CR
city: Firenze
country: Italy
facility: AOU Careggi - Cardiologia Generale 1
state: FI
city: Genova
country: Italy
facility: IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia
state: GE
city: Grosseto
country: Italy
facility: Ospedale della Misericordia - UO Cardiologia
state: GR
city: Sanremo
country: Italy
facility: Presidio Ospedaliero - UO Cardiologia
state: IM
city: Lecco
country: Italy
facility: Ospedale Alessandro Manzoni - SCD Cardiologia
state: LC
city: Lucca
country: Italy
facility: Ospedale Campo Marte - UO Cardiologia
state: LU
city: Desio
country: Italy
facility: Ospedale di Circolo - UOC Cardiologia - UTIC
state: MB
city: Monza
country: Italy
facility: Ospedale San Gerardo - UO Cardiologia UTIC
state: MB
city: Cinisello Balsamo
country: Italy
facility: Ospedale Bassini - UO Cardiologia e UTIC
state: MI
city: Legnano
country: Italy
facility: Ospedale Civile - UTIC - Cardiologia
state: MI
city: Milano
country: Italy
facility: Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC
state: MI
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico - Divisione di Cardiologia
state: MI
city: Milano
country: Italy
facility: Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC
state: MI
city: Milano
country: Italy
facility: Ospedale San Paolo - Divisione di Cardiologia
state: MI
city: Milano
country: Italy
facility: Ospedale San Luca - Centro Auxologico - UO Cardiologia
state: MI
city: Milano
country: Italy
facility: Ospedale San Carlo Borromeo - Cardiologia UCC
state: MI
city: Milano
country: Italy
facility: Ospedale L. Sacco - Divisione di Cardiologia
state: MI
city: Milano
country: Italy
facility: Ospedale Niguarda - Cardiologia 1 - Emodinamica
state: MI
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas - UO Cardiologia Interventistica e UTIC
state: MI
city: Mantova
country: Italy
facility: Presidio Ospedaliero Carlo Poma - UO Cardiologia
state: MN
city: Nuoro
country: Italy
facility: Ospedale San Francesco - Cardiologia UTIC
state: NU
city: Olbia
country: Italy
facility: Ospedale Giovanni Paolo II - UTIC Cardiologia
state: OT
city: Piacenza
country: Italy
facility: Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia
state: PC
city: Padova
country: Italy
facility: Azienda Ospedaliera Padova - Clinica Cardiologica
state: PD
city: Pisa
country: Italy
facility: AOU Pisana - UO Malattie Cardiovasc. 1-Cisanello
state: PI
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - Card. con UCC-Lab. Ricerca Sperim. Card.
state: PV
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova - UO Degenza Cardiologica
state: RE
city: Roma
country: Italy
facility: AO San Giovanni Addolorata - Cardiologia 2
state: RM
city: Rimini
country: Italy
facility: Ospedale Infermi - UO Cardiologia
state: RN
city: Salerno
country: Italy
facility: AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC
state: SA
city: Torino
country: Italy
facility: AOU San Giovanni Battista - SCDU Cardiologia 1
state: TO
city: Trieste
country: Italy
facility: AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara
state: TS
city: Treviso
country: Italy
facility: Ospedale Ca' Foncello - UOC Cardiologia
state: TV
city: Busto Arsizio
country: Italy
facility: Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia
state: VA
city: Saronno
country: Italy
facility: Presidio Ospedaliero di Saronno - UOC Cardiologia
state: VA
city: Varese
country: Italy
facility: Ospedale di Circolo Fondazione Macchi - SSD Unità di Cure Intensive Coronariche
state: VA
city: Mestre
country: Italy
facility: Ospedale dell'Angelo - UO Cardiologia
state: VE
city: Viterbo
country: Italy
facility: Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica
state: VT
city: Napoli
country: Italy
facility: AORN Cardarelli - UO SC Cardiologia con UTIC
city: Napoli
country: Italy
facility: AOU Federico II - UTIC
city: Novara
country: Italy
facility: AO Univ. Maggiore della Carità - Cardiologia 2
Study officials:
affiliation: Ospedale Alessandro Manzoni - Lecco
name: Felice Achilli, MD
role: STUDY_CHAIR
affiliation: Centro Cardiologico Monzino - Milano
name: Giulio Pompilio, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.