Efficacy of Early Administration of Clotinab in Acute Myocardial Infarction
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 4

Summary: 
      The ADMIRAL (Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute
      myocardial infarction) study demonstrated that early administration of abciximab in patients
      with ST elevation acute myocardial infarction prior to PCI improves clinical outcomes but no
      specifically designed randomized study has addressed the issue of early upstream use of GP
      IIb/IIIa inhibitors in ST elevation acute myocardial infarction who are undergoing PCI,
      especially in the era of routine pretreatment with 600 mg of clopidogrel. Therefore, the
      objective of the randomized ECLAT-STEMI study was to assess the hypothesis that the early
      upstream use of Clotinab is a useful therapy in patients with ST elevation MI undergoing PCI
      compared to "provisional use", even after pretreatment with a 600-mg loading dose of
      clopidogrel.
    

Detailed description: 
      It is well known that platelet-mediated thrombosis is account for the pathophysiology of
      acute coronary syndrome (ACS) (1,2). In the treatment of ACS, intravenous platelet
      glycoprotein (GP) IIb/IIIa receptor antagonists for platelet aggregation may reduce the risk
      of ischemic complications (3-7). Therefore, in the management of ACS, Platelet GP IIb/IIIa
      receptor inhibitors have been developed as a promising new therapy for the reduction of
      coronary events and the improvement of clinical outcomes.

      Abciximab, one of platelet GP IIb/IIIa receptor blockers, was developed by Coller in 1985 and
      named as 7E3(8). Abciximab is a chimeric human monoclonal antibody and binds to platelet
      surface GP IIb/IIIa receptor competitively with adhesive molecules such as fibrinogen and von
      Willebrand factor, and blocks the final stage of platelet aggregation(9). The effect of
      Abciximab has been proved in many clinical trials such as the EPIC trial(9), EPILOG
      trial(10), TARGET(11) etc. The contribution of GP IIb/IIIa inhibition in ACS (Tirofiban) is
      shown in placebo-controlled trials in which upstream GP IIb/IIIa inhibition was initiated
      upon admission (12,13). Although these results are encouraging, there are few other data to
      support the use of upstream GP IIb/IIIa inhibitors. Moreover, according to the GUSTO-IV trial
      (14), the use of Abciximab was not recommended in the manner of upstream use. To evaluate the
      role of abciximab in conservatively treated non-ST-elevation ACS patients, the GUSTO-IV study
      randomized 7800 patients with non-ST-elevation ACS to receive either placebo or an Abciximab
      bolus (0.25 mg/kg) and 24-hour or 48-hour infusion(0.125 µg/kg/min). However, in fact, a
      trend was noted for potential harm with the higher abciximab dose. Even subgroup analyses
      including high-risk troponin-positive patients showed no benefit with either abciximab
      regimen (9.7% with placebo, 10.2% with 24-hour abciximab, 11.7% with 48-hour abciximab for
      death or MI at 30 days, P = NS). Because of these results, the majority of patients received
      abciximab relatively late, at the time of PCI in clinical practices.

      However, the ADMIRAL study (3) demonstrated that early administration of abciximab in
      patients with ST elevation acute myocardial infarction prior to PCI improves clinical
      outcomes and also no specifically designed randomized study has addressed the issue of early
      upstream use of GP IIb/IIIa inhibitors in ST elevation acute myocardial infarction who are
      undergoing PCI, especially in the era of routine pretreatment with 600 mg of clopidogrel.
      Therefore, the objective of the randomized ECLAT-STEMI study was to assess the hypothesis
      that the early upstream use of Clotinab is a useful therapy in patients with ST elevation MI
      undergoing PCI compared to "provisional use", even after pretreatment with a 600-mg loading
      dose of clopidogrel.

      The Clotinab, a product made in ISU ABXIS CO., LTD, was produced by inserting anti- platelet
      GP IIb/IIIa DNA into Chinese hamster's ovary cell. Since it contains identical active
      ingredient as ReoPro® on the domestic market, it is expected that the Clotinab has same
      efficacy to ReoPro® as a platelet GP IIb/IIIa receptor inhibitor. Recently, the Clotinab is
      shown to be safe and effective in preventing ischemic heart complications for high-risk
      patients who will undergo PCI.

      2. Study Protocol 2-1. Objectives: Randomized, controlled, single blind, multi-center trial
      To assess the hypothesis that the early upstream use of Clotinab is a useful therapy in
      patients with ST elevation myocardial infarction undergoing PCI compared to "provisional
      use", even after pretreatment with a 600-mg loading dose of clopidogrel.

      2-2. Study Design: Efficacy of CLotinab in ST-elevation Acute myocardial infarction Trial -
      ST Elevation Myocardial Infarction (The ECLAT - STEMI study)

      2-3. Study Endpoints:

        1. Primary Endpoint: Efficacy To evaluate the effect of early upstream use of Clotinab
           (started at emergency room) co-administered with clopidogrel loading dose 600mg in STEMI

           - 30 Days MACCE (death, MI, TVR, cerebrovascular event)

        2. Secondary Endpoint: Efficacy and Safety To evaluate the safety of early upstream use of
           Clotinab (started at emergency room) co-administered with clopidogrel loading dose 600mg
           in STEMI

             -  TIMI flow at before and after PCI

             -  Corrected TIMI frame count after PCI

             -  Procedural success (No reflow incidence)

             -  MACCE at 9 month

             -  Major bleeding event (According to TIMI criteria)

             -  9 month Angiography Finding
    

Intervention name(s): Clotinab; Clotinab
Intervention type(s): Drug; Drug
Intervention description(s): Clotinab: IV bolus 0.25 mg per Kg and a 12-hour IV infusion 0.125 μg per kg; Clotinab: IV bolus 0.25 mg per Kg and a 12-hour IV infusion 0.125 μg per kg
Other intervention name(s): Clotinab, Gp IIb/IIIa inhibitor; Clotinab, Gp IIb/IIIa inhibitor
Intervention MeSH terms: Abciximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Angioplasty; Transluminal; Percutaneous Coronary