Acute Ischemic Stroke MedDRA version: 8.1 Level: LLT Classification code 10055221 Term: Ischemic stroke
Conditions
Interventions
Product Name: Microplasmin
Product Code: M-PLA-P07-REC/40-a
Pharmaceutical Form: Solution for infusion
Current Sponsor code: M-PLA-P07-REC/40-a
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
ThromboGenics Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Acute ischemic stroke (defined as a measurable neurological deficit of sudden onset considered secondary to focal cerebral ischemia and not otherwise attributable to ICH or other condition), with onset within 12 hours before start of study drug administration (Onset is defined as the time the patient was last seen in a normal state, or bedtime for unwitnessed strokes occurring during the night). 2. Evidence of perfusion defect of at least 2 cm in diameter, as assessed by MRI (PWI) corresponding to the acute stroke syndrome. The PWI will be assessed by relative mean transit time (MTT) images. 3. Ability to initiate study drug administration within 1 hour of completion of MRI and within 12 hours of stroke onset. 4. Male or female age 18-85 (inclusive) 5. Patients with baseline NIHSS >= 4 and ==65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: General exclusion criteria 1. 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 2. Symptoms suggestive of subarachnoid hemorrhage, even if CT scan or MRI is negative for hemorrhage 3. Women known to be pregnant, lactating, or having a positive or indeterminate pregnancy test Stroke related exclusion criteria 4. Neurological deficit that has led to stupor or coma (NIHSS Level Of Consciousness Item 1a score >or=2) 5. High clinical suspicion of septic embolus 6. Thrombosis involving cerebral veins 7. Rapidly improving neurological signs at any time before initiation of study drug administration Imaging related exclusion criteria 8. Hemorrhagic transformation or intracerebral hemorrhage observed on baseline CT of the brain or gradient recalled echo (GRE) magnetic resonance imaging 9. CT or MRI evidence of nonvascular cause for the neurological symptoms 10. Ischemic lesion consistent with lacunar stroke 11. PWI not obtained or uninterpretable 12. No MTT defect corresponding to acute stroke deficit 13. Large hypodensity on CT involving > 1/3 of the MCA territory 14. Baseline DWI volume > 1/3 of the MCA territory 15. Signs of mass effect causing shift of midline structures on CT or MRI 16. Unable to undergo MRI (i.e., ferrous implants, cardiac pacemakers, agitation, claustrophobia or known sensitivity to MRI contrast agents) Safety related exclusion criteria 17. Congenital or acquired coagulopathy causing either of the following a. activated partial thromboplastin time prolongation greater than 2 seconds above the ULN for local laboratory b. International normalized ratio of 1.4 or more. 18. 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. 19. History of stroke within the previous 3 months 20. Seizures at any time between stroke onset to planned initiation of study drug 21. History of intracranial hemorrhage 22. History of surgery, lumbar puncture, biopsy or trauma to internal organs within the previous 30 days. 23. Major trauma at the time of stroke 24. Head trauma within the previous 90 days. 25. Known bleeding diathesis. 26. Baseline platelet count 400mg/dl or <50 mg/dl if administration of glucose does not rapidly reverse neurological deficit Exclusion criteria that may potentially interfere with outcome assessment 28. Life expectancy <3 months 29. Other serious illness that in the opinion of the investigator may confound clinical assessment (e.g. hepatic, cardiac, or renal failure, advanced cancer) Exclusion criteria related to concomitant medication 30. If treatment with tPA is indicated (IN THE 0-3 POST-STROKE TIME WINDOW) 31. Treatment with rtPA or any other thrombolytic agent for the qualifying stroke 32. Administration of intra-arterial or systemic thrombolytic therapy in previous 7 days 33. Need for antiplatelet agent, unfractionated or heparin-related products, direct thrombin inhibitor, oral anticoagulant within 24 hours after treatment bolus. 34. Treatment with low molecular weight heparin, direct thrombin inhibitor, or GPIIb/IIIa antagonists within 48 hours prior to randomisation 35. Treatment with vitamin-K antagonis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and efficacy of microplasmin administered intravenously in patients with acute ischemic stroke;Secondary Objective: None;Primary end point(s): STUDY ENDPOINTS SAFETY EVALUATIONS/CRITERIA The safety profile of three dose regimens of microplasmin administered intravenously in patients with acute ischemic stroke will be defined based on the rate of occurrence of: Safety parameters: · Intracranial hemorrhage*, · Major bleeding **, · Bleeding other than major, · Serious and non-serious adverse events***, · Allergic reactions, · Hypotension, or other vital sign alterations during treatment · 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) * Asymptomatic (by CT at 24 hours and GRE at 7 days) or symptomatic (accompanied by NIHSS increase of >= 2 points within 36 hours).The CT scan may be replaced by an MRI if this is consistent with local standards; however, if bleeding is evident on the MRI, a CT-scan MUST be performed. ** 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; clinical intracranial hemorrhage. *** In the context of this study, an increase in NIHSS score of 4 points or more from the baseline score is defined as a Serious Adverse Event. EFFICACY EVALUATIONS/CRITERIA Efficacy parameters · NIHSS total score at 30 days (or last rating) adjusted for baseline NIHSS total score . Proportion of patients who achieve an NIHSS total score at 30 days (or last rating) of 1 or less or who show an improvement from baseline in NIHSS total score of at least 8 points or more. · Change from ba | — |
Countries
Austria, Belgium, Germany, United Kingdom
Outcome results
None listed