Presentation on theme: "STEM-AMI OUTCOME TRIAL STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial A national, multicentre, randomised, open-label, Phase."— Presentation transcript:
1STEM-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
2What is G-CSF? Granulocyte Colony Stimulating Factor GlycoproteinGrowth factorCytokineProduced by endothelium, macrophages and other immune cellsG-CSF receptor present on precursor cells in the bone marrowInitiates proliferation and differentiation into mature granulocytesStimulates bone marrow cell release into circulation
3Two important G-CSF uses MOST COMMON: Post chemotherapy febrile neutropeniaPotent inducer of hematopoietic stem cell mobilization for stem cell transplantation
12STEM-AMI OUTCOME TRIAL STUDY OBJECTIVESTo 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
13STEM-AMI OUTCOME TRIAL DESIGNPhase 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.TREATMENTFILGRASTIM 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.
14STEM-AMI OUTCOME TRIAL PRIMARY EFFICACY END POINTClinical outcome will be assessed by the composite endpoint of:death orrecurrence of MI orhospitalization due to heart failureSAFETY ENDPOINTSIncidence and severity of bleeding complicationsIncidence of malignancyIncidence and intensity of AEs and SAEs
15STEM-AMI OUTCOME TRIAL INCLUSION CRITERIAPatients 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 ≥2Evidence of LV dysfunction (EF biplane ≤ 45%) ≤ 24 h after revascularizationMen and women aged ≥18 years and ≤ 75 years,Informed consent must be signed before proceeding with any study procedure.
16STEM-AMI OUTCOME TRIAL EXCLUSION CRITERIAPrevious anterior MIRecent MI (within 1 month)Known previous LV dysfunction (EF <45%),Angiographic evidence of coronary anatomy not suitable for PCIValve disease requiring surgical correctionHistory of previous cardiac surgery or PCI on LAD within 6 monthsPrevious or current documented history of leukemia, myeloproliferative or myelodisplastic disorder, malignant diseaseHaemoglobin <10 mg/dlWhite blood cells (WBC) > mm3Platelet < mm3SepsisKnown HIV infectionImmune system diseasesInterstitial lung diseaseSerious concomitant medical conditions (other than ischemic heart disease)Pregnancy and breast feedingDocumented alcohol and drug abuseAnticipated poor complianceCurrent participation in a clinical trial with other investigational products or cell therapyEMOCROMOHb <10 g/dlGlobuli bianchi >25.000/mm3Piastrine <50.000/mm3ANAMNESI EXTRACARDIACAMalattie mieloproliferative, leucemiaNeoplasieHIVPatologia autoimmuneInterstiziopatia polmonareGravidanza o allattamentoAbuso di alcool e/o drogheScarsa complianceANAMNESI CARDIOLOGICAPregresso IMA anterioreIMA nel mese precedenteNota disfunzione VSx (FE ≤ 45% )Valvulopatia con indicazione CCHPregressa CCH nei 6 mesi precedentiPregressa PCI su IVA nei 6 mesi precedenti
18STEM-AMI OUTCOME TRIAL ASSESMENT I DAY -1/0Screening and randomizationObtain written informed consentDocumented acute anterior STEMIDocumented primary PCI/PCI-rescue (symptom to ballon time)TIMI flow post-PCI registrationEvidence of Echo Simpson biplane EF ≤45%, EDV and ESVHemochrome (hemoglobin, platelets, WBC)Pregnancy test (if necessary)Determine patient’s eligibility for enrollmentRandomization to study treatment group
19STEM-AMI OUTCOME TRIAL ASSESMENT II DAY 0-7In Hospital phaseG-CSF administrationHemochrome (WBC count)Documentation of ADRs/SAEsECGECHO: EF (Echo Simpson biplane), EDV and ESV
20STEM-AMI OUTCOME TRIAL ASSESMENT III DAY 301-month visitClinical EvaluationDocumentation of ADRs/SAEsECG
21STEM-AMI OUTCOME TRIAL ASSESMENT IV DAY 1806-months visitClinical EvaluationDocumentation of ADRs/SAEsECGECHO: EF (Echo Simpson biplane), EDV and ESV
22STEM-AMI OUTCOME TRIAL ASSESMENT V DAY 36512-months visitPhone interviewDocumentation of ADRs/SAEs
23STEM-AMI OUTCOME TRIAL ASSESMENT V DAY 73024-months visitClinical EvaluationDocumentation of ADRs/SAEsECGECHO: EF (Echo Simpson biplane), EDV and ESV
24STEM-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 ANMCOGrazie per l’attenzione