1. STEM-AMI OUTCOME TRIAL STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial   A national, multicentre, randomised, open-label, Phase III study Dott. Luca Deferrari U.O. Cardiologia IRCCS San Martino, Genova

2. What is G-CSF? Granulocyte Colony Stimulating Factor
Glycoprotein
Growth factor
Cytokine
Produced by endothelium, macrophages and other immune cells
G-CSF receptor present on precursor cells in the bone marrow
Initiates proliferation and differentiation into mature granulocytes
Stimulates bone marrow cell release into circulation

3. Two important G-CSF uses
MOST COMMON: Post chemotherapy febrile neutropenia
Potent inducer of hematopoietic stem cell mobilization for stem cell transplantation

4. Side effects associated with G-CSF

5. STEM–AMI Outcome trial: rationale

6. STEM–AMI Outcome trial: rationale

7. STEM–AMI Outcome trial: rationale

8. STEM –AMI Outcome trial: rationale

9. STEM–AMI Outcome trial: rationale

10. STEM–AMI Outcome trial: rationale

11. STEM–AMI Outcome trial: rationale

12. STEM-AMI OUTCOME TRIAL
STUDY OBJECTIVES
To demonstrate that G-CSF in addition to state of the art treatment is safe and significantly improves clinical outcome in patients with reduced left ventricular EF (≤45%) after successful reperfusion for large anterior acute myocardial infarction

13. STEM-AMI OUTCOME TRIAL
DESIGN
Phase III, randomized, open label.
1530 Patients (50 centres) will be randomized to standard therapy + G-CSF or standard therapy alone in 1:1 ratio.
Accrual time 3 years. Follow-up time 2 years.
TREATMENT
FILGRASTIM 5 µg/kg will be administered subcutaneously bis in die for 6 days (from Day 1 to Day 6), starting within 24 h after PCI and reperfusion.

14. STEM-AMI OUTCOME TRIAL
PRIMARY EFFICACY END POINT
Clinical outcome will be assessed by the composite endpoint of:
death or
recurrence of MI or
hospitalization due to heart failure
SAFETY ENDPOINTS
Incidence and severity of bleeding complications
Incidence of malignancy
Incidence and intensity of AEs and SAEs

15. STEM-AMI OUTCOME TRIAL
INCLUSION CRITERIA
Patients affected by acute anterior STEMI undergoing primary PCI (or PCI-rescue with persistent occlusion of coronary artery)
Time symptom-to-balloon ≥3 h and ≤12h (or ≤24 h if symptoms persist)
TIMI flow post PCI ≥2
Evidence of 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.

16. STEM-AMI OUTCOME TRIAL
EXCLUSION CRITERIA
Previous anterior MI
Recent MI (within 1 month)
Known previous LV dysfunction (EF <45%),
Angiographic evidence of coronary anatomy not suitable for PCI
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 myelodisplastic disorder, malignant disease
Haemoglobin <10 mg/dl
White blood cells (WBC) > mm3
Platelet < 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 or cell therapy
EMOCROMO
Hb <10 g/dl
Globuli bianchi >25.000/mm3
Piastrine <50.000/mm3
ANAMNESI EXTRACARDIACA
Malattie mieloproliferative, leucemia
Neoplasie
HIV
Patologia autoimmune
Interstiziopatia polmonare
Gravidanza o allattamento
Abuso di alcool e/o droghe
Scarsa compliance
ANAMNESI CARDIOLOGICA
Pregresso IMA anteriore
IMA nel mese precedente
Nota disfunzione VSx (FE ≤ 45% )
Valvulopatia con indicazione CCH
Pregressa CCH nei 6 mesi precedenti
Pregressa PCI su IVA nei 6 mesi precedenti

17. STEM-AMI OUTCOME TRIAL
Assessment I
Assessment II
Assessment
III
Assessment IV
Assessment V
Assessment VI
Day -1/0
In hospital
phase
1 month
6 months
12 months
24 months

18. STEM-AMI OUTCOME TRIAL
ASSESMENT I DAY -1/0
Screening and randomization
Obtain written informed consent
Documented acute anterior STEMI
Documented primary PCI/PCI-rescue (symptom to ballon time)
TIMI flow post-PCI registration
Evidence of Echo Simpson biplane EF ≤45%, EDV and ESV
Hemochrome (hemoglobin, platelets, WBC)
Pregnancy test (if necessary)
Determine patient’s eligibility for enrollment
Randomization to study treatment group

19. STEM-AMI OUTCOME TRIAL
ASSESMENT II DAY 0-7
In Hospital phase
G-CSF administration
Hemochrome (WBC count)
Documentation of ADRs/SAEs
ECG
ECHO: EF (Echo Simpson biplane), EDV and ESV

20. STEM-AMI OUTCOME TRIAL
ASSESMENT III DAY 30
1-month visit
Clinical Evaluation
Documentation of ADRs/SAEs
ECG

21. STEM-AMI OUTCOME TRIAL
ASSESMENT IV DAY 180
6-months visit
Clinical Evaluation
Documentation of ADRs/SAEs
ECG
ECHO: EF (Echo Simpson biplane), EDV and ESV

22. STEM-AMI OUTCOME TRIAL
ASSESMENT V DAY 365
12-months visit
Phone interview
Documentation of ADRs/SAEs

23. STEM-AMI OUTCOME TRIAL
ASSESMENT V DAY 730
24-months visit
Clinical Evaluation
Documentation of ADRs/SAEs
ECG
ECHO: EF (Echo Simpson biplane), EDV and ESV

24. STEM-AMI OUTCOME TRIAL
Egregi Dottori, Con la presente, comunichiamo che oggi, 8 novembre 2013, è stato arruolato il primo paziente dello Studio STEM-AMI Outcome dall'Ospedale San Gerardo di Monza. Cordialmente Segreteria Organizzativa Centro di Coordinamento Centro Studi ANMCO
Grazie per l’attenzione