Why Abciximab and Reteplase Preclinical and pilot clinical studies suggest that the combination of a IIb/IIIa inhibitor and a thrombolytic may: Accelerate reperfusion Prevent reocclusion Improve clinical outcome Facilitate PCI Protect the microcirculation and improve the microcirculatory flow
GUSTO-IV AMI Rationale The primary hypothesis to be tested is that Abciximab added to reduced dose Reteplase will improve clinical outcomes with equal or superior safety compared to conventional thrombolysis with Reteplase alone.
GUSTO-IV AMI Study Objective The primary objective of this study is to compare the effects of Abciximab (bolus + infusion) in combination with Reteplase (5 U + 5 U double bolus) and low-dose weight adjusted heparin (treatment), versus 10 U +10 U double bolus Reteplase with standard heparin (control) on the primary endpoint of all-cause mortality through 30 days.
GUSTO-IV AMI Trial Design Phase III Multicenter, Multinational Randomized Open label Approximately 800 sites Approximately 16,600 patients
GUSTO-IV AMI Trial Protocol (n = 16,600) ST, lytic eligible, < 6 hr ASA No Abciximab 2 x 10 U bolus (30’) Reteplase Abciximab* Low Dose Heparin: 60 U/kg bolus followed by a 7 U/kg/hr infusion 1º endpoint: mortality at 30 days 2º endpoint: clinical and safety events at 30 days 2 x 5 U bolus (30’) Reteplase Standard Heparin: 5,000 U bolus followed by either 800 U/hr (pts < 80 kg) or 1,000 U/hr (pts > 80 kg) infusion * 0.25 mg/kg bolus followed by 0.125 g/kg/min infusion for 12 hours
GUSTO-IV AMI Major Inclusion Criteria At least 18 years of age Prolonged (> 30 minutes), continuous, ischemic pain with onset within 6 hours prior to randomization ECG changes –> 2 mm ST-segment elevation in 2 or more contiguous leads –> 1 mm ST-segment elevation in 2 or more limb leads Written informed consent
GUSTO-IV AMI Major Exclusion Criteria Planned primary percutaneous intervention Active internal bleeding or history of hemorrhagic diathesis Major surgery or serious trauma within the previous 6 weeks History of cerebrovascular accident within the previous 2 years Administration of oral anticoagulants within the previous 7 days
GUSTO-IV AMI Laboratory Procedures Baseline (within 6 hours prior to randomization) –Hemoglobin –Hematocrit –Platelet count –aPTT, PT or INR Baseline (within 2 hours prior to randomization) –CK-MB (or Total CK if CK-MB not available) –12-lead ECG Post Procedure –ECG (hospital discharge or day 7; prior to transfer; or 12-24 hrs post revascularization procedure)
GUSTO-IV AMI Efficacy and Safety Endpoints All cause mortality at 30 days Non-fatal disabling stroke through discharge or day 7 post-randomization (whichever is earlier) All cause mortality through 1 year Incidence of hemorrhagic stokes (including hemorrhagic conversion) through discharge or day 7 post-randomization (whichever is earlier)