E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062025 |
E.1.2 | Term | Intracerebral haematoma evacuation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
To investigate the safety of minimally invasive surgery plus aspiration followed by the administration of a low dose of recombinant tissue plasminogen activator (rt-PA; Activase, Genentech, Inc., San Francisco, CA) to intracerebral hemorrhage patients (ICH) via a catheter inserted directly into the clot and to assess its ability to remove blood clot from the brain tissue |
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E.2.2 | Secondary objectives of the trial |
To test if the intervention facilitates more rapid and complete recovery of function and decreased mortality compared to conventional medical management without subjecting the patient to craniotomy. |
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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 |
Tier 3 has been changed from 3mg dose in the main study to a substudy aiming to demonstrate that Intraoperative stereotactic CT-guided Endoscopic Surgery (ICES) is a feasible, safe, and technically effective treatment for patients with acute intracerebral hemorrhage. (14 Oct 2008). THIS SUBSTUDY IS NOT BEING UNDERTAKEN IN EUROPE - IT IS ONLY BEING UNDERTAKEN IN SPECIFIC CENTRES IN USA. |
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E.3 | Principal inclusion criteria |
1. Age 18-80 2. GCS < 14 or a NIHSS > 6; 3. Spontaneous supratentorial ICH > 20cc; 4. Symptoms less than 12 hours prior to diagnostic CT scan (an unknown time of symptom onset is exclusionary); 5. Intention to initiate surgery within 48 hours after diagnostic CT; 6. First dose can be given within 54 hours after diagnostic CT (delays for post surgical stabilization of catheter bleeding or because of unanticipated surgical delay are acceptable with approved waiver from the coordinating center); 7. Six-hour clot size equal to the most previous clot size + 5 cc (as determined by an additional CT scan at least 6 hours after the initial stability scan (A*B*C)/2 method); 8. SBP < 200 mmHg sustained for 6 hours recorded closest to the time of randomization; 9. Historical Rankin score of 0 or 1; 10. Negative pregnancy test. |
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E.4 | Principal exclusion criteria |
1. Infratentorial hemorrhage (any involvement of the midbrain or lower brainstem as demonstrated by radiograph or complete third nerve palsy); 2. Patients with platelet count < 100,000, INR > 1.3, or an elevated PT or APTT (reversal of coumadin is permitted but the patient must not require coumadin during the acute hospitalization). Irreversible coagulopathy either due to medical condition or prior to randomization (patient must have a sustained INR ≤ 1.3 using short- and long-acting procoagulants [such as but not limited to NovoSeven, FFP, and/or vitamin K]); 3. Clotting disorders; 4. Any concurrent serious illness that would interfere with the safety assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, and hematologic disease; 5. Patients with a mechanical valve; 6. Patients with unstable mass or evolving intracranial compartment syndrome; 7. Ruptured aneurysm, AVM, vascular anomaly, Moyamoya disease; 8. Irreversibly impaired brainstem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS less than or equal to 4; 9. Intraventricular hemorrhage requiring external ventricular drainage; 10. Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts; 11. Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention; 12. Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis; 13. In the investigator’s opinion, the patient is unstable and would benefit from a specific intervention rather than supportive care plus or minus endoscopic or MIS+rtPA removal of the ICH; 14. Prior enrollment in the study; 15. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated; 16. Participation in another simultaneous trial of ICH treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1.) 30-day mortality 2.) procedure related mortality 3.) incidence of cerebritis, meningitis 4.) rate of rebleeding |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Dose finding: three different doses in separate tiers. best risk/benefit dose for safety testing |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
surgery plus drug versus conventional medical management (surgery/no drug) |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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The time of the six month assessment of the last person recruited into 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 | 6 |