Clinical trial NCT00841438: Efficacy of Early Administration of Clotinab in Acute Myocardial Infarction
Official title: Efficacy of Clotinab in Acute Myocardial Infarction Trial- ST Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: Angioplasty
Transluminal
Percutaneous Coronary
Lead sponsor: Yonsei University
Sponsor class: OTHER
Collaborators: name: ISU ABXIS (Korea pharmaceutical company)
First posted: 2009-02-11
Enrollment: 786
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Eligibility criteria: Inclusion Criteria:

1. The patient must be at least 18-80 years of age.
2. The patient had the symptoms of acute myocardial infarction within 12 hours with ST segment elevation of more than 1 mm in at least two contiguous leads of EKG or new onset LBBB.
3. The patient or guardian agrees to the study protocol and provides informed, written consent.

Exclusion Criteria:

1. Patients to whom PCI can not be undergone within 12 hours from receiving the study drug
2. Cardiogenic shock or symptomatic hypotension or sitting SBP \< 95 mmHg
3. The history of major surgery, trauma, retinal hemorrhage, significant gastrointestinal or genitourinary bleeding within recent 6 weeks;
4. History of cerebrovascular attack within two years, or cerebrovascular attack with a significant residual neurological deficit
5. Severe or malignant hypertension (= sitting SBP \> 180 mmHg and/or sitting DBP \> 105 mmHg)
6. The patients who require oral anticoagulants during the trial; patients who have been administrated oral anticoagulants within 7 days
7. The history or diagnosis of vasculitis; renal insufficiency (the level of serum creatinine is two times higher than the upper limit of normal of each center)
8. The patients who could not take anti-platelet drugs
9. The patients who might die of other disease than cardiac disease during the trial.

Primary outcomes:
measure: MACCE (death, MI, TVR, cerebrovascular event)
timeFrame: 30 days
Secondary outcomes:
measure: MACCE (death, MI, TVR, cerebrovascular event)
timeFrame: 9 months
measure: TIMI flow at before and after PCI
timeFrame: Immediate post procedure
measure: Corrected TIMI frame count after PCI
timeFrame: Immediate postprocedure
Other outcomes:
Locations:
city: Cheonan
country: Korea, Republic of
facility: Dankook University Hospital
city: Cheonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Health Insurance Corporation Ilsan Hospital
city: Goyang
country: Korea, Republic of
facility: Dongguk University International Hospital
city: Goyang
country: Korea, Republic of
facility: Myongji Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Pusan
country: Korea, Republic of
facility: Inje University Pusan Paik Hospital
city: Pyungchon
country: Korea, Republic of
facility: Hallym University sacred Heart Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University East-West Nea Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Youngdong Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic University of Korea, kangnam St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Inje University Sanggye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic University of Korea, St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University kangnam sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Wonju
country: Korea, Republic of
facility: Wonju Christian Hospital
Study officials:
affiliation: Division of Cardiology, Cardiovascular Hospital, Yonsei University
name: Yangsoo Jang, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim JS, Park SM, Kim BK, Ko YG, Choi D, Hong MK, Seong IW, Kim BO, Gwon HC, Hong BK, Tahk SJ, Park SW, Kim CJ, Jeong MH, Yoon J, Jang Y; ECLAT-STEMI Trial investigators. Efficacy of clotinab in acute myocardial infarction trial-ST elevation myocardial infarction (ECLAT-STEMI). Circ J. 2012;76(2):405-13. doi: 10.1253/circj.cj-11-0676. Epub 2011 Dec 7.