Efficacy Of Eptifibatide Compared To Abciximab In Primary Percutaneous Coronary Intervention (PCI) For Acute ST Elevation Myocardial Infarction (STEMI)

Infarction, Myocardial Clinical Trial

Official title:

Eptifibatide Versus Abciximab in Primary PCI for Acute ST Elevation Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00426751
• Other study ID #: 106915
• Status: Completed
• Phase: Phase 3
• First received: January 24, 2007
• Last updated: November 21, 2012
• Start date: October 2006
• Est. completion date: December 2007

Study information

• Verified date: November 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: German Institute of Medical Documentation and Information
• Study type: Interventional

Clinical Trial Summary

Multinational, multicentre, randomised, prospective, open, parallel group study directly comparing two glycoprotein-IIb/IIIa inhibitors, abciximab and eptifibatide, added early to standard treatment before primary PCI of STEMI patients with respect to effect on sum-ST-resolution after 60 minutes post-procedure and other measures of myocardial reperfusion

Recruitment information / eligibility

• Status: Completed
• Enrollment: 429
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women must be postmenopausal (i.e.12 months without menstrual period), or surgically sterile, i.e. women of child bearing potential are not allowed to be included into the study. In cases of doubt a pregnancy test should be performed. (NB -post menopausal women currently receiving hormone replacement are permissible)

• Acute myocardial infarction < 12 h defined as:

1. Angina or equivalent symptoms > 20 min and

2. ST elevation in 2 contiguous ECG leads (= 2 mm precordial lead, = 1 mm limb lead). This ECG recording serves as baseline ECG, i.e. ECG I.

• Planned primary percutaneous coronary intervention

• The subject has given written informed, dated consent to participate in the study

Exclusion Criteria:

• Subjects not able to give informed consent

• Left Bundle Branch Block

• Thrombolytic therapy within 24 hours before randomization

• Oral anticoagulation with International Normalized Ratio (INR) > 2

• Known platelets < 100.000/µl or known hemorrhagic diathesis

• Stroke or Transient Ischemic Attack (TIA) within the past 6 months or any permanent residual neurological defect

• Evidence of an active gastrointestinal or urogenital bleeding

• Major surgery within 6 weeks

• History of allergic reaction to abciximab or eptifibatide or any component used in the study (including contrast media)

• Known severe renal (creatinine clearance <30ml/min) or hepatic insufficiency as well as Alanine transaminase (ALT)/aspartate transaminase (AST) elevations = 3xUpper limit normal (ULN); isolated AST-elevation is not considered an exclusion criteria from study participation

• Severe concomitant disease with life expectation < 1 year

• Subject has participated in any study using an investigational drug or device within 30 days or within 5 half-lives of the investigational drug (whichever is longer) of entry into this study.

• Subjects who will be inaccessible due to geographic or social factors during treatment or follow-up

• In France, a subject is neither affiliated with nor a beneficiary of a social security category.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Infarction, Myocardial
• Myocardial Infarction

Intervention

Drug:
• Abciximab
Intravenous bolus of 0.25 mg/kg followed by continuous intravenous infusion of 0.125 mcg/kg/min (max. 10 mcg/min) for 12 h after PCI.
• Eptifibatide
Intravenous bolus of 180 mcg/kg followed immediately by a continuous infusion of 2.0 mdg/kg/ min for 20-24 h after end of PCI, and a second bolus of 180 mcg/kg administered 10 min after the first bolus.

Locations

Country	Name	City	State
France	GSK Investigational Site	Alençon
France	GSK Investigational Site	Bordeaux
France	GSK Investigational Site	Caen Cedex 5
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Melun
France	GSK Investigational Site	Melun
France	GSK Investigational Site	Nancy
France	GSK Investigational Site	Ollioules
France	GSK Investigational Site	Pau
France	GSK Investigational Site	Perpignan
France	GSK Investigational Site	Pessac Cedex
France	GSK Investigational Site	Toulon
France	GSK Investigational Site	Vandoeuvre Les Nancy
Germany	GSK Investigational Site	Aachen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Homburg	Saarland
Germany	GSK Investigational Site	Ludwigshafen	Rheinland-Pfalz
Germany	GSK Investigational Site	Moenchengladbach	Nordrhein-Westfalen
Germany	GSK Investigational Site	Neuss	Nordrhein-Westfalen
Germany	GSK Investigational Site	Offenbach	Hessen
Germany	GSK Investigational Site	Wuerzburg	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Complete Sum ST Resolution (STR) 60 Minutes (Min) After Percutaneous Coronary Intervention (PCI) (Per Protocol Population)	Sum STR was calculated as the difference between baseline (ECG I) and ECG III. The sum STR is the segment elevation resolution from all ECG leads associated with the infarct location. ST resolution, a method used to evaluate myocardial reperfusion, was expressed as a percentage of the baseline value (Complete: = 70% resolution).	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Primary	Number of Participants With Complete Sum ST Resolution (STR) 60 Min After Percutaneous Coronary Intervention (PCI) (Intent-to-Treat Population)	Sum STR was calculated as the difference between baseline (ECG I) and ECG III. The sum STR is the segment elevation resolution from all ECG leads associated with the infarct location. ST resolution, a method used to evaluate myocardial reperfusion, was expressed as a percentage of the baseline value (Complete: = 70% resolution).	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Secondary	Number of Participants With Complete or Partial Sum ST Resolution (STR) 60 Min After PCI	Sum STR was calculated as the difference between baseline (ECGI) and ECG III. The sum STR is the segment elevation resolution from all ECG leads associated with infarct location. ST resolution, a method used to evaluate myocardial reperfusion, was expressed as a percentage of the baseline (Complete: = 70% resolution; Partial: = 30% and < 70% resolution; None: < 30% resolution).	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Secondary	Number of Participants With Complete Single Lead ST Resolution (STR) 60 Min After PCI	Single lead STR is calculated as the difference (as a percentage) between baseline (ECG I) and ECG III of either the ST elevation on one of the leads (II, III, aVF, V5, and V6) or the ST depression of one of the precordial leads (V1- V4), whichever lead showed the largest deviation either at baseline or at ECG III, respectively (Complete: = 70%; Partial: = 30% and <70%).	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Secondary	Mean Change From Baseline in the Sum ST Resolution 60 Min After PCI	Sum STR was calculated as the difference between baseline (ECGI) and ECG III. The sum STR is the segment elevation resolution from all ECG leads associated with infarct location. ST resolution, a method used to evaluate myocardial reperfusion, was expressed as a percentage of the baseline.	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Secondary	Mean Change From Baseline in Single Lead ST Resolution (STR) 60 Min After PCI	Single lead STR is calculated as the difference between baseline (ECG I) and ECG III of either the ST elevation on one of the leads (II, III, aVF, V5, and V6) or the ST depression of one of the precordial leads (V1 -V4), whichever lead showed the largest deviation either at baseline or at follow-up, respectively. STR was expressed as a percentage from baseline.	Baseline (ECG I) and 60 min +/- 15 min after PCI (ECG III)	No
Secondary	Mean Change From Baseline in the Sum ST Resolution (STR) Before PCI	Mean sum STR was calculated as the difference between baseline (ECGI) and ECG II: the mean of the sum of ST elevation resolution from all ECG leads associated with infarct location. ST resolution was expressed as a percentage from baseline.	Baseline (ECG I) and immediately prior to PCI (ECG II)	No
Secondary	Mean Maximum ST Deviation Existing (Max STE) 60 Min After PCI	Max STE is measured similarly to single-lead STR, but was not compared with the ST deviation on the baseline ECG I. It was the existing ST deviation on the single ECG lead of maximum ST deviation present at 60 minutes after the PCI (ECG III).	60 min +/- 15 min after PCI (ECG III)	No
Secondary	Number of Participants With the Indicated Patency of Infarcted Vessels According to Thrombolysis in Myocardial Infarction (TIMI) Classification Before PCI	Number of participants with the respective patency of the infarcted vessels was evaluated by TIMI (Thrombolysis In Myocardial Infarction) flow grades (Grade 0 = No perfusion, Grade 1 = Penetration with minimal perfusion, Grade 2 = Partial perfusion, Grade 3 = Complete perfusion), as assessed by core angiography lab.	immediately before PCI	No
Secondary	Number of Participants With TIMI 3 Patency of Infarcted Vessels Following PCI	The number of participants with TIMI grade 3 (complete perfusion) patency of the infarcted vessels following PCI, as assessed by core angiography lab, was measured.	after PCI	No
Secondary	Mean Number of Corrected TIMI Frame Counts (cTIMI) Following PCI	cTIMI frame counts (number of cineframes needed for dye to reach standardized distal landmarks in a coronary vessel; objective index of coronary blood flow) following PCI, as assessed by core angiography lab.	after PCI	No
Secondary	Number of Participants With the Indicated Myocardial Blush Grade (TIMI Myocardial Perfusion Grade [TMPG]) After PCI	The number of participants with the indicated myocardial blush grade (TMPG), used to assess the myocardial reperfusion in the infarcted myocardium following PCI (as assessed by the core angiography laboratory), was measured. Blush grades: 0 = failure of dye to enter the microvasculature; 1 = dye slowly enters but fails to exit the microvasculature; 2 = delayed entry and exit of dye from the microvasculature; 3: normal entry and exit of dye from the microvasculature. Blush that is of only mild intensity throughout the washout phase but fades minimally is also classified as grade 3.	after PCI	No
Secondary	Combined Endpoint: Number of Participants With Events of Death, Re-myocardial Infarction (MI), and Urgent Target Vessel Revascularisation (UTVR)	The number of participants who died, experienced re-MI, or experienced UTVR (necessity of re-PCI of the target vessel or coronary artery bypass graft [CABG] because of recurrent ischaemic angina within 30 days after PCI) within the specified timeframe was measured.	Day 7 or hospital discharge; Day 30 after index-MI	No
Secondary	Number of Participants Who Died, and/or Experienced Re-MI and UTVR (Individually Counted)	The number of participants who died, and/or experienced re-MI or UTVR (individually counted) within the specified timeframe was measured.	Day 7 or hospital discharge; Day 30 after index-MI	No
Secondary	Number of Participants Who Experienced Stroke or Major Bleeding Complications	Number of participants who experienced stroke (hemorrhagic, non-hemorrhagic) or major bleedings (TIMI class: intracranial haemorrhage, spontaneous bleeding, bleeding at any instrumented site, retroperitoneal bleeding, or clinically significant overt haemorrhage associated with a drop in haematocrit of = 15% or a drop in haemoglobin of = 5 g/dL).	Day 7 or hospital discharge; Day 30 after index-MI	No
Secondary	Number of Participants Who Died and or Experienced Re-MI Until 6 Months After PCI	The number of participants who died and/or experienced re-MI within 6 month after PCI was measured.	until 6 Month (Day 180) after index-MI	No
Secondary	Number of Participants With Heart Failure Until 6 Months After PCI	The number of participants with heart failure within 6 month after PCI was measured.	until 6 Months (Day 180) after index-MI	No
Secondary	Number of Participants With Major Bleedings (TIMI Classification)	Number of participants with major bleedings (according to TIMI classification: intracranial haemorrhage, spontaneous bleeding, bleeding at any instrumented site, retroperitoneal bleeding, or clinically significant overt haemorrhage associated with a drop in haematocrit of = 15% or a drop in haemoglobin of = 5 g/dL) within the specified timeframe was measured.	Day 7 or hospital discharge; Day 30 after index-MI	No
Secondary	Number of Participants With Minor Bleedings (TIMI Classification)	The number of participants with minor bleedings (according to TIMI classification: clinically overt bleeding [e.g., gross haematuria or haematemesis) associated with a drop in haematocrit of = 9% or a drop in haemoglobin of = 3 g/dL) within the specified timeframe was measured.	Day 7 or hospital discharge; Day 30 after index-MI	No
Secondary	Mean Duration of Stay in the Ward	Costs were measured as the duration of stay in the ward (outpatient, normal ward, and intensive care unit) within the specified timeframe was measured.	until 6 months after index-MI	No