STEM-AMI OUTCOME TRIAL

STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

 A national, multicentre, randomised, open-label, Phase III study

Dott. Luca DeferrariU.O. Cardiologia

IRCCS San Martino, Genova

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

Two important G-CSF uses

1. MOST COMMON: Post chemotherapy febrile neutropenia

2. Potent inducer of hematopoietic stem cell mobilization for stem cell transplantation

Side effects associated with G-CSF

STEM–AMI Outcome trial: rationale

STEM–AMI Outcome trial: rationale

STEM–AMI Outcome trial: rationale

STEM –AMI Outcome trial: rationale

STEM–AMI Outcome trial: rationale

STEM–AMI Outcome trial: rationale

STEM–AMI Outcome trial: rationale

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

STEM-AMI OUTCOME TRIAL

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.

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

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.

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) >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 or cell therapy

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

ANAMNESI EXTRACARDIACA

•Malattie mieloproliferative, leucemia

•Neoplasie

•HIV

•Patologia autoimmune

•Interstiziopatia polmonare

•Gravidanza o allattamento

•Abuso di alcool e/o droghe

•Scarsa compliance

EMOCROMO

•Hb <10 g/dl

•Globuli bianchi >25.000/mm3

•Piastrine <50.000/mm3

STEM-AMI OUTCOME TRIAL

Day -1/0 In hospital phase

1 month 12 months 24 months

Assessment I

Assessment II

Assessment III

Assessment IV

Assessment V

Assessment VI

6 months

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

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

STEM-AMI OUTCOME TRIAL

ASSESMENT III DAY 30

1-month visit

• Clinical Evaluation

• Documentation of ADRs/SAEs

• ECG

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

STEM-AMI OUTCOME TRIAL

ASSESMENT V DAY 365

12-months visit

• Phone interview

• Documentation of ADRs/SAEs

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

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.

CordialmenteSegreteria Organizzativa

Centro di Coordinamento Centro Studi ANMCO

Grazie per l’attenzione