ACUTE INTRACRANIAL VERTEBROBASILAR ARTERY OCCLUSION RESULTING IN ACUTE ISCHEMIC STROKE MedDRA version: 8.1 Level: LLT Classification code 10048963 Term: Basilar artery occlusion
Conditions
Interventions
Product Name: Microplasmin
Product Code: M-PLA-P10/40
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Microplasmin
Current Sponsor code: M-PLA-P10/40
Concentration unit: mg/ml milligra
Sponsors
ThromboGenics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. New neurologic signs in the vertebrobasilar artery distribution allowing initiation of study drug treatment within 24 hours of the onset of neurological symptoms (loss of consciousness, dysarthria, anarthria, hemianopia, tetraparesis, tetraplegia, bilateral Babinski sign, dysphagia, double vision, nystagmus); other non-specific neurological symptoms such as dizziness, headache, vomiting, nausea are not restricted to the 24 hour time window 2. Patients with angiographically documented vertebrobasilar artery occlusion 3. Age 18-75 (inclusive). 4. Women of child-bearing potential must have a negative pregnancy test prior to enrolment and be using a reliable form of contraception 5. For conscious patients, prior to inclusion in the study and following a full explanation of the nature and purpose of the study, the patient or the patient’s legal representative must consent/assent to participate by signing the Informed Consent document. For unconscious patients or patients whose legal representative cannot be contacted or where it is not possible to obtain consent in advance of enrolment in the study, consent must be obtained as soon as possible after inclusion. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with coma >6 hrs duration and complete loss of brain stem reflexes (corneal reflex, gag reflex, VOR, pupil reflexes) as measured at the last assessment before sedation/intubation 2. Rapidly improving neurologic signs at any time before initiation of study drug administration. 3. Known contrast agent-sensitivity 4. Uncontrolled hypertension defined as a systolic blood pressure > 180 mm Hg or a diastolic blood pressure > 100 mm Hg on 3 separate occasions at least 10 minutes apart or requiring continuous IV therapy. 5. History of stroke within the previous 6 weeks. 6. Seizures at any time between stroke onset to planned initiation of study drug. 7. History of intracranial hemorrhage 8. History of surgery, lumbar puncture, biopsy or trauma to internal organs within the previous 30 days. 9. Head trauma within the previous 90 days. 10. Known bleeding diathesis. 11. Baseline INR >1.7 or baseline APTT > 2 times normal 12. Baseline platelet count 400mg/dl 15. Patients who have received intra-arterial or systemic thrombolytic therapy within the 7 days prior to the study. 16. Patients who have received tPA or any other thrombolytic agent for the qualifying stroke. 17. Patients receiving vitamin-K antagonists or heparin which results in either an INR>1.4 or an aPTT>2 times control (ULN for the hospital laboratory), respectively. 18. Patients who have received glycoprotein IIb/IIIa inhibitors within 48 hours prior to enrolment. 19. Patients who have received more than one dose of low molecular weight heparin within 48 hours prior to enrolment. 20. Participation in another study with an investigational drug or device within the previous 30 days, prior participation in the present study, or planned participation in another trial within the timeframe of the current trial 21. Life expectancy <3 months 22. Other serious illness that in the opinion of the investigator may confound clinical assessment (eg hepatic, cardiac, or renal failure, advanced cancer)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and the arterial recanalization potential of microplasmin when administered intra-arterially in patients with acute intracranial vertebrobasilar artery occlusion;Secondary Objective: None;Primary end point(s): STUDY ENDPOINTS SAFETY EVALUATIONS/CRITERIA The safety profile of a single dose regimen of microplasmin administered intra-arterially in patients with acute intracranial vertebrobasilar stroke will be defined based on the rate of occurrence of: Safety parameters: · Intracranial hemorrhage, · Major bleeding *, · Bleeding other than major, · Reocclusion at 48 hr after initiation of study drug (as determined by CT angiography), · Serious and non-serious adverse events, · Allergic reactions, · Immunology (Microplasmin and Staphylokinase antibody assays) · Laboratory data · Markers of systemic lysis (fibrinogen, plasminogen, D-dimer, PT and aPTT) and complement activation C3, C4 and CH50) * In the context of this study major bleeding is defined as any bleeding event resulting in death; any retroperitoneal hemorrhage; overt bleeding associated with a need for transfusion of 2 or more units of blood or which requires surgical intervention; overt bleeding associated with a decrease from baseline in hemoglobin of at least 2.0 g/dL. EFFICACY EVALUATIONS/CRITERIA Primary efficacy endpoint · Proportion of patients achieving recanalization of the basilar artery (defined as an improvement of at least one TIMI grade*) at the end of study drug administration * TIMI 0: no reperfusion TIMI 1: reperfusion without distal branch filling TIMI 2: reperfusion with incomplete or slow distal branch filling TIMI 3: full perfusion Secondary efficacy endpoints · Duration of study drug administration to achieve recanalization . Proportion of patient achieving TIMI 3 and TIMI 2 or 3 grade at the end of study drug administration · Survival at day 90 · NIHSS total score at 90 days (or last rating) adjusted for baseline N | — |
Countries
Germany
Outcome results
None listed