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Early Rapid Reversal of Platelet Thrombosis With Intravenous Elinogrel Before PCI to Optimize Reperfusion in Acute Myocardial Infarction - ERASE MI
Description:
Various studies have demonstrated the utility of the adjunctive use of P2Y12 inhibitors for ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). The current trial is a phase II trial designed to study the safety and efficacy of escalating doses of intravenous elinogrel, a novel P2Y12 inhibitor, in the treatment of STEMI patients undergoing PPCI.
Hypothesis:
Elinogrel would be safe and efficacious in the treatment of STEMI patients undergoing PPCI, as compared with placebo.
Study Design
Study Design:
Patients Enrolled: 70
Mean Follow Up: 30 days
Mean Patient Age: 47-65 years
Female: 17
Patient Populations:
- Age ≥18 years
- Persistent ST-segment elevation ≥1 mm (≥0.1 mV) in two contiguous limb leads or ≥2 mm (≥0.2 mV) in two contiguous precordial leads
- Ischemic chest pain or equivalent ischemic symptoms ≥20 minutes with onset within 6 hours of hospital presentation
Exclusions:
- Age >75 years
- Estimated or actual weight <55>
- Cardiogenic shock (systolic blood pressure <90 mm="" hg="" requiring="" vasopressor="" or="" hemodynamic="">
- Uncontrolled hypertension
- New or old left bundle branch block
- History of prior ischemic stroke or cerebral arteriovenous malformation
Primary Endpoints:
- Safety and tolerability of escalating doses of elinogrel pre-PPCI for STEMI
- TIMI major and minor bleeding
- GUSTO severe and moderate bleeding
- Intracranial hemorrhage through 30 days
Secondary Endpoints:
- % ST resolution before first device activation during PPCI
- cTFC in the infarct-related artery on the initial diagnostic angiogram before PPCI
- % ST resolution 30 minutes post-PPCI
Drug/Procedures Used:
The trial was conducted in two stages. Part 1 of the trial was denoted as the dose-escalation phase. The first dose group (10 mg) included 10 subjects, whereas the other dose groups (20, 40, and 60 mg) each evaluated 20 subjects. Part 2 of the ERASE MI trial was designed as a dose confirmation study using the highest tolerated dose from part 1.
Concomitant Medications:
All patients received aspirin, unfractionated heparin, and clopidogrel (loading dose 600 mg, maintenance dose 75 mg daily). In addition, a repeat dose of 300 mg clopidogrel loading dose was mandated for all subjects 4 hours after completion of PCI. Use of other anticoagulants, including low molecular weight heparin, bivalirudin, or fondaparinux, was not permitted. Glycoprotein IIb/IIIa inhibitor use was strongly recommended (84%).
Principal Findings:
A total of 70 patients were enrolled, 35 to elinogrel, and 35 to placebo. Baseline characteristics were fairly similar between the two groups. All patients underwent angiography after randomization, and 64 patients (91.4%) underwent PPCI. The median first door-to-balloon times ranged from 61 to 88 minutes. The trial was terminated early due to administrative reasons on behalf of the sponsor.
Per-protocol analyses are reported. On pre-PCI angiography, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (cTFC) <100 was="" similar="" between="" placebo="" (21.4%)="" vs.="" elinogrel="" 10="" mg="" (50%)="" vs.="" elinogrel="" 20="" mg="" (10%),="" vs.="" elinogrel="" 40="" mg="" (0%)="" vs.="" elinogrel="" 60="" mg="" (30%)="" (p="ns)." timi="" 3="" flow="" pre-angiography="" was="" also="" similar="" between="" the="" various="" arms="" (21.4%="" vs.="" 50%="" vs.="" 20%="" vs.="" 0%="" vs.="" 20%,="" p="ns)." similarly,="" on="" post-pci="" angiography,="" timi="" 3="" flow="" was="" noted="" at="" a="" similar="" rate="" in="" the="" five="" arms="" (71.4%="" vs.="" 100%="" vs.="" 80%="" vs.="" 90%="" vs.="" 60%,="" p="ns)." bleeding="" outcomes="" were="" also="" similar="" between="" the="" five="" arms.="" there="" were="" no="" deaths="" or="" repeat="" mis="" in="" any="" of="" the="" patients;="" one="" stroke="" was="" noted="" in="" the="" placebo="" arm.="" was="" similar="" between="" placebo="" (21.4%)="" vs.="" elinogrel="" 10="" mg="" (50%)="" vs.="" elinogrel="" 20="" mg="" (10%),="" vs.="" elinogrel="" 40="" mg="" (0%)="" vs.="" elinogrel="" 60="" mg="" (30%)="" (p="NS)." timi="" 3="" flow="" pre-angiography="" was="" also="" similar="" between="" the="" various="" arms="" (21.4%="" vs.="" 50%="" vs.="" 20%="" vs.="" 0%="" vs.="" 20%,="" p="NS)." similarly,="" on="" post-pci="" angiography,="" timi="" 3="" flow="" was="" noted="" at="" a="" similar="" rate="" in="" the="" five="" arms="" (71.4%="" vs.="" 100%="" vs.="" 80%="" vs.="" 90%="" vs.="" 60%,="" p="NS)." bleeding="" outcomes="" were="" also="" similar="" between="" the="" five="" arms.="" there="" were="" no="" deaths="" or="" repeat="" mis="" in="" any="" of="" the="" patients;="" one="" stroke="" was="" noted="" in="" the="" placebo="" arm.="">
Interpretation:
This is a small and prematurely terminated trial, which provides some feasibility and tolerability data regarding the use of a single dose of elinogrel, a novel intravenous P2Y12 antagonist, in the treatment of patients with STEMI undergoing PPCI. Larger phase 3 trials are necessary before any consideration regarding the use of this drug clinically.
References:
Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: The Early Rapid ReversAl of Platelet ThromboSis with Intravenous Elinogrel before PCI to Optimize REperfusion in Acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009;158:998-1004.e1.
Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Chest Pain, Thrombosis, Blood Platelets, Angioplasty, Balloon, Coronary
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