E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population will consist of up to 452 male and female subjects with anterior STEMI and occluded proximal or mid LAD with TIMI 0, 1 or 2 flow with indication for primary PCI. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000904 |
E.1.2 | Term | Acute myocardial infarction, of other anterior wall |
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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 |
The primary objective of the study is to demonstrate that among subjects undergoing primary PCI for anterior STEMI treated with a bivalirudin monotherapy anticoagulation strategy, the intracoronary infusion of an abciximab bolus with or without thrombus aspiration prior to stent implantation, compared to no infusion with or without thrombus aspiration (standard of care), results in 1) reduced infarct size measured by cardiac MRI at 30 days (range -7 days/+14 days; i.e., between 23 and 44 days), 2) reduce microvascular obstruction (MVO) by cardiac MRI at 5 + 2 days (i.e., between 3 and 7 days), 3) enhanced ST-segment resolution, 4) improved myocardial perfusion, 5) reduced thrombus burden and angiographic complications, and 6) no increase in major and minor bleeding. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to demonstrate that among patients undergoing primary PCI for anterior STEMI treated with a bivalirudin monotherapy anticoagulation strategy with thrombus aspiration compared to no thrombus aspiration prior to stent implantation with or without abciximab bolus results in 1) reduced infarct size and MVO measured by cardiac MRI, 2) enhanced ST-segment resolution, 3) improved myocardial perfusion, 4) reduced thrombus burden and angiographic complications and 5) reduced microvascular obstruction (MVO) by cardiac MRI at 5 + 2 days (i.e., between 3 and 7 days). |
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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 Sub-study: a cardiac MRI sub-study evaluating microvascular obstruction (MVO) will be performed with up to 160 subjects at up to 30 sites. |
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E.3 | Principal inclusion criteria |
1. The subject must be ≥ 18 years of age; 2. Subject is experiencing clinical symptoms consistent with AMI (e.g., chest pain, arm pain, etc.,) >30 minutes duration and unresponsive to nitroglycerin; 3. Anterior MI with ECG showing at least 1 mm of ST-segment elevation in 2 or more contiguous leads in V1-V4, or new (or presumably new) left bundle branch block; 4. Anticipated symptom onset to balloon or aspiration time of ≤ 5 hours; 5. The subject and his/her physician are willing to comply with specified follow-up evaluations; 6. The subject or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided and signed written informed consent, approved by the appropriate Medical Ethics Committee (MEC) or Institutional Review Board (IRB). 7. Infarct artery located in the proximal or mid left anterior descending coronary artery, with TIMI 0, 1 or 2 flow at the time of initial diagnostic angiography (prior to wire passage); 8. Based on coronary anatomy, PCI is indicated for revascularization; 9. Only one epicardial coronary artery will be treated; 10. Expected ability to deliver a ClearWay™ RX Infusion Catheter to the infarct lesion (absence of excessive tortuosity, diffuse disease or moderate/heavy calcification). |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following index procedure. 2. Prior myocardial infarction, or known prior systolic dysfunction (known ejection fraction <40% by any prior measure or regional wall motion abnormalities); 3. An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first twelve months post enrollment; 4. Subjects who have prior history of coronary artery bypass graft surgery (CABG); 5. Subjects who previously underwent coronary stent implantation and in whom coronary angiography demonstrates stent thrombosis to be the cause of the AMI; 6. Subject has previously undergone an angioplasty or stenting procedure in the left anterior descending artery; 7. Definite planned use of aspiration, atherectomy, thrombectomy and/or distal protection catheters prior to PTCA or stent implantation (other than in subjects randomized to thrombus aspiration); 8. Any contraindication to undergo MRI imaging. 9. Impaired renal function (creatinine clearance <30 ml/min/1.73m² [or <51.99 cc/min estimated with the Cockcroft-Gault formula]) or on dialysis; 10. Known platelet count <100,000 cells/mm³ or >700,000 cells/mm³ or a Hgb <10g/dL; 11. Intended intracoronary infusion of supersaturated oxygen; 12. Subject has active bleeding or a history of bleeding diathesis or coagulopathy or refusal to receive blood transfusions if necessary; 13. History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; 14. Stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect; 15. Gastrointestinal or genitourinary bleeding within the last 2 months, or major surgery within six weeks; 16. Subject has received any organ transplant or is on a waiting list for any organ transplant; 17. Subject has other medical illness that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy of less than one year; 18. Subject has a known hypersensitivity or contraindication to abciximab, aspirin, bivalirudin, clopidogrel, ticlopidine or prasugrel; 19. Subject has a known hypersensitivity or allergy to stainless steel, nickel, cobalt chromium, nitinol, titanium or known hypersensitivity or allergy to contrast media (e.g. rash) that cannot effectively be controlled by premedication with steroids and/or diphenhydramine. Subjects with hypersensitivity or allergy to any of the components of the device (structural, drug or polymer components) and subjects with true prior anaphylaxis to contrast media should not be enrolled; 20. Prior administration of thrombolytic therapy, GP IIb/IIIa inhibitors, low molecular weight heparin or fondaparinux for this admission. Subjects receiving prior unfractionated heparin may be enrolled; 21. Current use of coumadin or coumarin; 22. Subjects presenting with cardiogenic shock (SBP <80 mmHg for >30 minutes, or requiring IV pressors or emergency IABP for hypotension treatment) or cardiopulmonary resuscitation prior to randomization; 23. Subject has received >5000 units of unfractionated heparin within the preceding 24 hours prior to presenting to the catheterization laboratory, or any subject who receives heparin after arrival in the cardiac catheterization laboratory prior to randomization; 24. Any significant medical condition which in the Investigator's opinion may interfere with the subject‟s optimal participation in the study; 25. Currently participating in another investigational drug or device study, which has not completed the primary endpoint follow-up period; 26. Previous enrollment in this study. 27. Coronary anatomy such that coronary artery bypass graft surgery will possibly be required within 30 days; 28. Multivessel intervention required during the index procedure; 29. Severe vessel tortuosity, diffuse disease or severe calcification is present which may impede successful delivery of the ClearWay™ RX Infusion Catheter or the Export ® Aspiration Catheter; 30. Features are present highly unfavorable for PCI; 31. MI is due to thrombosis within or adjacent to a previously implanted stent; 32. Left ventriculography demonstrates severe mitral regurgitation or a VSD; 33. Unprotected left main stenosis >40% or that will require intervention. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Infarct size (percentage of total LV mass) at 30 days (range -7 days/+14 days; i.e., between 23 to 44 days) measured by cardiac MRI, comparing the pooled randomized active (abciximab) infusion (with or without thrombus aspiration) to the pooled non infusion arms (with or without thrombus aspiration). |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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Subjects will be followed clinically in-hospital, at 30 days (range -7 days/+14 days; i.e., between 23 and 44 days) and at 12 months (± 28 days) following the index procedure. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |