E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myocardial infarctio |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To investigate the effect of pre-treatment with 25 µg/kg bolus and maintenance infusion Tirofiban on the amount of residual cumulative ST deviation 1 hour after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel ). |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the effect or pre-treatment with a high bolus dosage of Tirofiban on the incidence of death, recurrent MI, thrombotic bail-out or urgent TVR at 30 days follow-up, compared to no pre-treatment
2. To investigate the effect of pre-hospital pre-treatment with a high bolus dosage of Tirofiban on the incidence of major bleeding
3. To investigate the effect of pre-hospital pre-treatment with a high bolus dosage of Tirofiban on the incidence of TIMI 3 flow of the infarct related vessel (IRV) at initial angiography. 4. To investigate the effect of pre-treatment with a high bolus dosage of Tirofiban on the incidence of myocardial perfusion as assessed by Myocardial Blush Grade scoring immediately after primary angioplasty, compared to no pre-treatment
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MRI Core laboratory: 2006-09-14 OnTIME-2 Spect Substudy: 2006-09-14 OnTIME-2 Platelet Function Substudy: 2006-09-14 |
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E.3 | Principal inclusion criteria |
1. Males or females > 21 years of age and < 85 years with symptoms of acute myocardial infarction of more than 30 minutes but less than 24 hours. 2. ST segment elevation of > 1 mV in 2 adjacent ECG leads, with cumulative ST segment deviation of 6 mm or more. 3. Patients should only be included if there is a reasonable expectation that PCI will be conducted within 2 hours.
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E.4 | Principal exclusion criteria |
1) Patients who are unable to give informed consent or have life expectancy of < 1year 2) Patient is pregnant or breastfeeding 3) Patients with left bundle branch block 4) Subject who have received thrombolytic therapy within 24 hours or warfarin in last 7 days or another GpIIb/IIIa within last 30 days 5) Subject who have known severe renal dysfunction (GFR<30ml/min or serum creatinine >2.5 mg/dl or 200mmmol/l) or receiving dialysis or previously undertaken renal transplantation 6) Confirmed or persistent severe hypertension (Systolic b.p. > 180 mmHg and/or diastolic b.p. >110 mmHg) at randomization 7) Subjects with a contraindication to anticoagulation or at increased bleeding risk a. Past or present history (<1 year) of bleeding from gastrointestinal (haematemesis) malena, frank bleed in stool or visible haematuria b. Known thrombocytopenia, platelet count (<100,00/mm3 ) or coagulopathy or platelet disorder c. History of hemorrhagic TIA, CVA (last 6 months), intracranial pathology (neoplasm, aneurysm, AV malformation) d. History of major recent (<30 day) surgery or trauma e. Known presence of retinopathy or pericarditis or recent epidural procedure 8) Patients who have received another investigational drug or device or participated in any clinical trial within 4 weeks prior to randomization 9) Patients in cardiogenic shock (SBP ,80mmHg for >30 mins) or needing IABP 10) Known Hb <11gm/dl or HCT <33% 11) Hypersensitivity to any component of Tirofiban or ASA or Heparin or clopidogrel
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E.5 End points |
E.5.1 | Primary end point(s) |
All ECG assessments will be made by an independent ECG core lab (Diagram, Zwolle, the Netherlands). Measurements will be made by 2 readers blinded to clinical and angiographic data and the time of ECG recording as well as the randomization scheduled. The absolute level of the ST segment deviation will be measured by digital caliper to the nearest 0.01mv 20ms after the end of the QRS interval using the TP segment as isoclectic baseline. Residual cumulative ST segment deviation calculation is detailed below.
1. To investigate the effect of pre-treatment with 25 µg/kg bolus and maintenance infusion Tirofiban on the amount of residual cumulative ST deviation 1 hour after Primary Coronary Angioplasty for acute myocardial infarction, compared to no pre-treatment (besides Aspirin, Heparin and 600 mg of Clopidogrel ).
Residual cumulative ST segment deviation (STres): ECG’s are done 1 hr after PCA. Patients with right bundle- branch block who clearly have ST-segment-elevations are included in the analysis. All ECG's are analyzed by an independent Core lab, including those ECG’s from patients who did not undergo angioplasty (candidates for CABG or conservative treatment). The sum of ST-segment-deviation in all 12 leads will be measured 20 ms after the end of the QRS complex with a caliper.
The sum of residual ST segment deviation is classified into 4 groups (37) 0 mm: normalized ST segment: defined as no residual ST-segment deviation 1 - 3 mm: defined as residual ST-segment deviation between 1 and 3 mm 4 - 6 mm: defined as residual ST-segment deviation between 4 and 6 mm > 7 mm: defined as a residual ST-segment deviation more than 7 mm.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 24 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |