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STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial (STEM-AMI)

Primary Purpose

Anterior Acute Myocardial Infarction, Left Ventricular Systolic Dysfunction

Status
Terminated
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
G-CSF administration
Sponsored by
Heart Care Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anterior Acute Myocardial Infarction

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ospedali Riuniti - SOD Cardiologia Ospedaliera e UTIC
  • Ospedale Generale Provinciale CG Mazzoni - Divisione di Cardiologia
  • Ospedale San Donato - UO Cardiologia
  • AORN Giuseppe Moscati - UO Cardiologia-UTIC
  • Humanitas Gavazzeni - UO Cardiologia
  • Ospedale Bolognini - Divisione di Cardiologia
  • Ospedale Maggiore - UO Cardiologia
  • Ospedale Sant'Elia - Cardiologia-UTIC
  • Ospedale Moriggia Pelascini - UO Cardiologia
  • Ospedale Sant'Anna - UOC Cardiologia
  • Ospedale Maggiore - UO Cardiologia e UTIC
  • Istituti Ospitalieri - UO Cardiologia
  • AOU Careggi - Cardiologia Generale 1
  • IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia
  • Ospedale della Misericordia - UO Cardiologia
  • Presidio Ospedaliero - UO Cardiologia
  • Ospedale Alessandro Manzoni - SCD Cardiologia
  • Ospedale Campo Marte - UO Cardiologia
  • Ospedale di Circolo - UOC Cardiologia - UTIC
  • Ospedale San Gerardo - UO Cardiologia UTIC
  • Ospedale Bassini - UO Cardiologia e UTIC
  • Ospedale Civile - UTIC - Cardiologia
  • Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC
  • Ospedale Maggiore Policlinico - Divisione di Cardiologia
  • Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC
  • Ospedale San Paolo - Divisione di Cardiologia
  • Ospedale San Luca - Centro Auxologico - UO Cardiologia
  • Ospedale San Carlo Borromeo - Cardiologia UCC
  • Ospedale L. Sacco - Divisione di Cardiologia
  • Ospedale Niguarda - Cardiologia 1 - Emodinamica
  • Istituto Clinico Humanitas - UO Cardiologia Interventistica e UTIC
  • Presidio Ospedaliero Carlo Poma - UO Cardiologia
  • Ospedale San Francesco - Cardiologia UTIC
  • Ospedale Giovanni Paolo II - UTIC Cardiologia
  • Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia
  • Azienda Ospedaliera Padova - Clinica Cardiologica
  • AOU Pisana - UO Malattie Cardiovasc. 1-Cisanello
  • Fondazione IRCCS Policlinico San Matteo - Card. con UCC-Lab. Ricerca Sperim. Card.
  • Arcispedale Santa Maria Nuova - UO Degenza Cardiologica
  • AO San Giovanni Addolorata - Cardiologia 2
  • Ospedale Infermi - UO Cardiologia
  • AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC
  • AOU San Giovanni Battista - SCDU Cardiologia 1
  • AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara
  • Ospedale Ca' Foncello - UOC Cardiologia
  • Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia
  • Presidio Ospedaliero di Saronno - UOC Cardiologia
  • Ospedale di Circolo Fondazione Macchi - SSD Unità di Cure Intensive Coronariche
  • Ospedale dell'Angelo - UO Cardiologia
  • Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica
  • AORN Cardarelli - UO SC Cardiologia con UTIC
  • AOU Federico II - UTIC
  • AO Univ. Maggiore della Carità - Cardiologia 2

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

G-CSF administration

standard therapy

Arm Description

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

Standard therapy

Outcomes

Primary Outcome Measures

The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure.

Secondary Outcome Measures

- 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.

Full Information

First Posted
October 22, 2013
Last Updated
February 2, 2021
Sponsor
Heart Care Foundation
Collaborators
A. Manzoni Hospital, Centro Cardiologico Monzino
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1. Study Identification

Unique Protocol Identification Number
NCT01969890
Brief Title
STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial
Acronym
STEM-AMI
Official Title
Phase III Study on STem cElls Mobilization in Acute Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Upon DSMC suggestion due to a too low enrollment rate.
Study Start Date
October 2013 (undefined)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heart Care Foundation
Collaborators
A. Manzoni Hospital, Centro Cardiologico Monzino

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anterior Acute Myocardial Infarction, Left Ventricular Systolic Dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
532 (Actual)

8. Arms, Groups, and Interventions

Arm Title
G-CSF administration
Arm Type
Experimental
Arm Description
Granulocyte Colony-Stimulating Factor (G-CSF) administration - 5 microg/kg subcutaneous every 12 hours for 6 days
Arm Title
standard therapy
Arm Type
No Intervention
Arm Description
Standard therapy
Intervention Type
Drug
Intervention Name(s)
G-CSF administration
Other Intervention Name(s)
Zarzio
Intervention Description
Zarzio - 5 microg/kg bis in die for 6 days
Primary Outcome Measure Information:
Title
The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure.
Time Frame
two years
Secondary Outcome Measure Information:
Title
- All cause death and cardiovascular events
Description
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.
Time Frame
two years
Other Pre-specified Outcome Measures:
Title
Safety endpoints - Incidence and severity of bleeding complications, - incidence of malignancy, - incidence and intensity of serious adverse events (SAEs) and adverse drug reactions (ADRs)
Time Frame
two years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felice Achilli, MD
Organizational Affiliation
Ospedale Alessandro Manzoni - Lecco
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Giulio Pompilio, MD
Organizational Affiliation
Centro Cardiologico Monzino - Milano
Official's Role
Study Chair
Facility Information:
Facility Name
Ospedali Riuniti - SOD Cardiologia Ospedaliera e UTIC
City
Ancona
State/Province
AN
ZIP/Postal Code
60122
Country
Italy
Facility Name
Ospedale Generale Provinciale CG Mazzoni - Divisione di Cardiologia
City
Ascoli Piceno
State/Province
AP
ZIP/Postal Code
63100
Country
Italy
Facility Name
Ospedale San Donato - UO Cardiologia
City
Arezzo
State/Province
AR
ZIP/Postal Code
52100
Country
Italy
Facility Name
AORN Giuseppe Moscati - UO Cardiologia-UTIC
City
Avellino
State/Province
AV
ZIP/Postal Code
83100
Country
Italy
Facility Name
Humanitas Gavazzeni - UO Cardiologia
City
Bergamo
State/Province
BG
ZIP/Postal Code
24125
Country
Italy
Facility Name
Ospedale Bolognini - Divisione di Cardiologia
City
Seriate
State/Province
BG
ZIP/Postal Code
24068
Country
Italy
Facility Name
Ospedale Maggiore - UO Cardiologia
City
Bologna
State/Province
BO
ZIP/Postal Code
40133
Country
Italy
Facility Name
Ospedale Sant'Elia - Cardiologia-UTIC
City
Caltanissetta
State/Province
CL
ZIP/Postal Code
93100
Country
Italy
Facility Name
Ospedale Moriggia Pelascini - UO Cardiologia
City
Gravedona
State/Province
CO
ZIP/Postal Code
22015
Country
Italy
Facility Name
Ospedale Sant'Anna - UOC Cardiologia
City
San Fermo della Battaglia
State/Province
CO
ZIP/Postal Code
22020
Country
Italy
Facility Name
Ospedale Maggiore - UO Cardiologia e UTIC
City
Crema
State/Province
CR
ZIP/Postal Code
26013
Country
Italy
Facility Name
Istituti Ospitalieri - UO Cardiologia
City
Cremona
State/Province
CR
ZIP/Postal Code
26100
Country
Italy
Facility Name
AOU Careggi - Cardiologia Generale 1
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
IRCCS San Martino Ist. Ricerca sul Cancro - UO Cardiologia
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Ospedale della Misericordia - UO Cardiologia
City
Grosseto
State/Province
GR
ZIP/Postal Code
58100
Country
Italy
Facility Name
Presidio Ospedaliero - UO Cardiologia
City
Sanremo
State/Province
IM
ZIP/Postal Code
18038
Country
Italy
Facility Name
Ospedale Alessandro Manzoni - SCD Cardiologia
City
Lecco
State/Province
LC
ZIP/Postal Code
23900
Country
Italy
Facility Name
Ospedale Campo Marte - UO Cardiologia
City
Lucca
State/Province
LU
ZIP/Postal Code
55100
Country
Italy
Facility Name
Ospedale di Circolo - UOC Cardiologia - UTIC
City
Desio
State/Province
MB
ZIP/Postal Code
20832
Country
Italy
Facility Name
Ospedale San Gerardo - UO Cardiologia UTIC
City
Monza
State/Province
MB
ZIP/Postal Code
20900
Country
Italy
Facility Name
Ospedale Bassini - UO Cardiologia e UTIC
City
Cinisello Balsamo
State/Province
MI
ZIP/Postal Code
20092
Country
Italy
Facility Name
Ospedale Civile - UTIC - Cardiologia
City
Legnano
State/Province
MI
ZIP/Postal Code
20025
Country
Italy
Facility Name
Ospedale Fatebenefratelli e Oftalmico - Cardiologia e UCC
City
Milano
State/Province
MI
ZIP/Postal Code
20121
Country
Italy
Facility Name
Ospedale Maggiore Policlinico - Divisione di Cardiologia
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Centro Cardiologico Monzino - Terapia Intensiva Cardiologica UTIC
City
Milano
State/Province
MI
ZIP/Postal Code
20138
Country
Italy
Facility Name
Ospedale San Paolo - Divisione di Cardiologia
City
Milano
State/Province
MI
ZIP/Postal Code
20142
Country
Italy
Facility Name
Ospedale San Luca - Centro Auxologico - UO Cardiologia
City
Milano
State/Province
MI
ZIP/Postal Code
20149
Country
Italy
Facility Name
Ospedale San Carlo Borromeo - Cardiologia UCC
City
Milano
State/Province
MI
ZIP/Postal Code
20153
Country
Italy
Facility Name
Ospedale L. Sacco - Divisione di Cardiologia
City
Milano
State/Province
MI
ZIP/Postal Code
20157
Country
Italy
Facility Name
Ospedale Niguarda - Cardiologia 1 - Emodinamica
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Istituto Clinico Humanitas - UO Cardiologia Interventistica e UTIC
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Presidio Ospedaliero Carlo Poma - UO Cardiologia
City
Mantova
State/Province
MN
ZIP/Postal Code
46100
Country
Italy
Facility Name
Ospedale San Francesco - Cardiologia UTIC
City
Nuoro
State/Province
NU
ZIP/Postal Code
08100
Country
Italy
Facility Name
Ospedale Giovanni Paolo II - UTIC Cardiologia
City
Olbia
State/Province
OT
ZIP/Postal Code
07026
Country
Italy
Facility Name
Ospedale Civile "Guglielmo da Saliceto" - Divisione di Cardiologia
City
Piacenza
State/Province
PC
ZIP/Postal Code
29100
Country
Italy
Facility Name
Azienda Ospedaliera Padova - Clinica Cardiologica
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
AOU Pisana - UO Malattie Cardiovasc. 1-Cisanello
City
Pisa
State/Province
PI
ZIP/Postal Code
56124
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo - Card. con UCC-Lab. Ricerca Sperim. Card.
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Arcispedale Santa Maria Nuova - UO Degenza Cardiologica
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
42100
Country
Italy
Facility Name
AO San Giovanni Addolorata - Cardiologia 2
City
Roma
State/Province
RM
ZIP/Postal Code
00184
Country
Italy
Facility Name
Ospedale Infermi - UO Cardiologia
City
Rimini
State/Province
RN
ZIP/Postal Code
47900
Country
Italy
Facility Name
AOUS Giovanni Di Dio Ruggi D'Aragona - UOC UTIC
City
Salerno
State/Province
SA
ZIP/Postal Code
84131
Country
Italy
Facility Name
AOU San Giovanni Battista - SCDU Cardiologia 1
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
AOU Ospedali Riuniti - SOC Cardiologia - Ospedale Cattinara
City
Trieste
State/Province
TS
ZIP/Postal Code
34149
Country
Italy
Facility Name
Ospedale Ca' Foncello - UOC Cardiologia
City
Treviso
State/Province
TV
ZIP/Postal Code
31100
Country
Italy
Facility Name
Ospedale di Circolo di Busto Arsizio - Divisione di Cardiologia
City
Busto Arsizio
State/Province
VA
ZIP/Postal Code
21052
Country
Italy
Facility Name
Presidio Ospedaliero di Saronno - UOC Cardiologia
City
Saronno
State/Province
VA
ZIP/Postal Code
21047
Country
Italy
Facility Name
Ospedale di Circolo Fondazione Macchi - SSD Unità di Cure Intensive Coronariche
City
Varese
State/Province
VA
ZIP/Postal Code
21100
Country
Italy
Facility Name
Ospedale dell'Angelo - UO Cardiologia
City
Mestre
State/Province
VE
ZIP/Postal Code
30174
Country
Italy
Facility Name
Ospedale Belcolle - UOC Cardiologia UTIC Emodinamica
City
Viterbo
State/Province
VT
ZIP/Postal Code
01100
Country
Italy
Facility Name
AORN Cardarelli - UO SC Cardiologia con UTIC
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
AOU Federico II - UTIC
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
AO Univ. Maggiore della Carità - Cardiologia 2
City
Novara
ZIP/Postal Code
28100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
26386788
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.
Results Reference
background
PubMed Identifier
31138020
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.
Results Reference
background

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STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

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