A Multi-Centre, Double-Blind, Placebo-Controlled, Ascending-Dose, Clinical Trial of Intra-venous Microplasmin Administration in Patients with Acute Ischemic Stroke - MITI-IV

• Conditions: Acute Ischemic Stroke; MedDRA version: 9.1Level: LLTClassification code 10055221Term: Ischemic stroke

• Registration Number: EUCTR2005-001074-27-AT
• Lead Sponsor: ThromboGenics Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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 =< 22
6. 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.
7. Women of child-bearing potential must have a negative pregnancy test prior to enrolment and be using a reliable form of contraception
8. Patients must be ambulatory prior to stroke onset.
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

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 < 100 X 10 9/L.
27. Blood glucose > 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 randomi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified