Efficacy of Early Administration of Clotinab in Acute Myocardial Infarction

Myocardial Infarction Clinical Trial

— ECLAT-STEMI  

Official title:

Efficacy of Clotinab in Acute Myocardial Infarction Trial- ST Elevation Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00841438
• Other study ID #: ISU-CLT-07001
• Status: Completed
• Phase: Phase 4
• First received: February 10, 2009
• Last updated: May 3, 2010
• Start date: July 2007
• Est. completion date: December 2009

Study information

• Verified date: February 2009
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 786
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• Clotinab
Clotinab: IV bolus 0.25 mg per Kg and a 12-hour IV infusion 0.125 µg per kg
• Clotinab
Clotinab: IV bolus 0.25 mg per Kg and a 12-hour IV infusion 0.125 µg per kg

Locations

Country	Name	City	State
Korea, Republic of	Dankook University Hospital	Cheonan
Korea, Republic of	Chonbuk National University Hospital	Cheonju
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Dongguk University International Hospital	Goyang
Korea, Republic of	Myongji Hospital	Goyang
Korea, Republic of	National Health Insurance Corporation Ilsan Hospital	Goyang
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Inje University Pusan Paik Hospital	Pusan
Korea, Republic of	Pusan National University Hospital	Pusan
Korea, Republic of	Hallym University sacred Heart Hospital	Pyungchon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Catholic University of Korea, kangnam St. Mary's Hospital	Seoul
Korea, Republic of	Catholic University of Korea, St. Mary's Hospital	Seoul
Korea, Republic of	Eulji General Hospital	Seoul
Korea, Republic of	Gachon University Gil Medical Center	Seoul
Korea, Republic of	Hallym University kangnam sacred Heart Hospital	Seoul
Korea, Republic of	Inje University Sanggye Paik Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Kyung Hee University East-West Nea Medical Center	Seoul
Korea, Republic of	Kyung Hee University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Yonsei University	Seoul
Korea, Republic of	Yonsei University Youngdong Severance Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Wonju Christian Hospital	Wonju

Sponsors (2)

Lead Sponsor	Collaborator
Yonsei University	ISU ABXIS (Korea pharmaceutical company)

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MACCE (death, MI, TVR, cerebrovascular event)		30 days	No
Secondary	MACCE (death, MI, TVR, cerebrovascular event)		9 months	No
Secondary	TIMI flow at before and after PCI		Immediate post procedure	No
Secondary	Corrected TIMI frame count after PCI		Immediate postprocedure	No