STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

Left Ventricular Systolic Dysfunction Clinical Trial

— STEM-AMI  

Official title:

Phase III Study on STem cElls Mobilization in Acute Myocardial Infarction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01969890
• Other study ID #: G112
• Status: Terminated
• Phase: Phase 3
• Start date: October 2013
• Est. completion date: May 2018

Study information

• Verified date: August 2018
• Source: Heart Care Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 532
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anterior Acute Myocardial Infarction
• Infarction
• Left Ventricular Systolic Dysfunction
• Myocardial Infarction

Intervention

Drug:
• G-CSF administration
Zarzio - 5 microg/kg bis in die for 6 days

Locations

Country	Name	City	State
Italy	Ospedali Riuniti - SOD Cardiologia Ospedaliera e UTIC	Ancona	AN
Italy	Ospedale San Donato - UO Cardiologia	Arezzo	AR
Italy	Ospedale Generale Provinciale CG Mazzoni - Divisione di Cardiologia	Ascoli Piceno	AP
Italy	AORN Giuseppe Moscati - UO Cardiologia-UTIC	Avellino	AV
Italy	Humanitas Gavazzeni - UO Cardiologia	Bergamo	BG
Italy	Ospedale Maggiore - UO Cardiologia	Bologna	BO
Italy	Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia	Busto Arsizio	VA
Italy	Ospedale Sant'Elia - Cardiologia-UTIC	Caltanissetta	CL
Italy	Ospedale Bassini - UO Cardiologia e UTIC	Cinisello Balsamo	MI
Italy	Ospedale Maggiore - UO Cardiologia e UTIC	Crema	CR
Italy	Istituti Ospitalieri - UO Cardiologia	Cremona	CR
Italy	Ospedale di Circolo - UOC Cardiologia - UTIC	Desio	MB
Italy	AOU Careggi - Cardiologia Generale 1	Firenze	FI
Italy	IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia	Genova	GE
Italy	Ospedale Moriggia Pelascini - UO Cardiologia	Gravedona	CO
Italy	Ospedale della Misericordia - UO Cardiologia	Grosseto	GR
Italy	Ospedale Alessandro Manzoni - SCD Cardiologia	Lecco	LC
Italy	Ospedale Civile - UTIC - Cardiologia	Legnano	MI
Italy	Ospedale Campo Marte - UO Cardiologia	Lucca	LU
Italy	Presidio Ospedaliero Carlo Poma - UO Cardiologia	Mantova	MN
Italy	Ospedale dell'Angelo - UO Cardiologia	Mestre	VE
Italy	Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC	Milano	MI
Italy	Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC	Milano	MI
Italy	Ospedale L. Sacco - Divisione di Cardiologia	Milano	MI
Italy	Ospedale Maggiore Policlinico - Divisione di Cardiologia	Milano	MI
Italy	Ospedale Niguarda - Cardiologia 1 - Emodinamica	Milano	MI
Italy	Ospedale San Carlo Borromeo - Cardiologia UCC	Milano	MI
Italy	Ospedale San Luca - Centro Auxologico - UO Cardiologia	Milano	MI
Italy	Ospedale San Paolo - Divisione di Cardiologia	Milano	MI
Italy	Ospedale San Gerardo - UO Cardiologia UTIC	Monza	MB
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	Ospedale San Francesco - Cardiologia UTIC	Nuoro	NU
Italy	Ospedale Giovanni Paolo II - UTIC Cardiologia	Olbia	OT
Italy	Azienda Ospedaliera Padova - Clinica Cardiologica	Padova	PD
Italy	Fondazione IRCCS Policlinico San Matteo - Card. con UCC-Lab. Ricerca Sperim. Card.	Pavia	PV
Italy	Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia	Piacenza	PC
Italy	AOU Pisana - UO Malattie Cardiovasc. 1-Cisanello	Pisa	PI
Italy	Arcispedale Santa Maria Nuova - UO Degenza Cardiologica	Reggio Emilia	RE
Italy	Ospedale Infermi - UO Cardiologia	Rimini	RN
Italy	AO San Giovanni Addolorata - Cardiologia 2	Roma	RM
Italy	Istituto Clinico Humanitas - UO Cardiologia Interventistica e UTIC	Rozzano	MI
Italy	AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC	Salerno	SA
Italy	Ospedale Sant'Anna - UOC Cardiologia	San Fermo della Battaglia	CO
Italy	Presidio Ospedaliero - UO Cardiologia	Sanremo	IM
Italy	Presidio Ospedaliero di Saronno - UOC Cardiologia	Saronno	VA
Italy	Ospedale Bolognini - Divisione di Cardiologia	Seriate	BG
Italy	AOU San Giovanni Battista - SCDU Cardiologia 1	Torino	TO
Italy	Ospedale Ca' Foncello - UOC Cardiologia	Treviso	TV
Italy	AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara	Trieste	TS
Italy	Ospedale di Circolo Fondazione Macchi - SSD Unità di Cure Intensive Coronariche	Varese	VA
Italy	Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica	Viterbo	VT

Sponsors (3)

Lead Sponsor	Collaborator
Heart Care Foundation	A. Manzoni Hospital, Centro Cardiologico Monzino

Country where clinical trial is conducted

Italy, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety endpoints - Incidence and severity of bleeding complications, - incidence of malignancy, - incidence and intensity of serious adverse events (SAEs) and adverse drug reactions (ADRs)		two years
Primary	The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure.		two years
Secondary	- All cause death and cardiovascular events	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.	two years