Intravenous Administration of Microplasmin for Treatment of Acute Ischemic Stroke

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00123305
• Date of registration: 21/07/2005
• Prospective Registration: Yes
• Primary sponsor: ThromboGenics
• Public title: Intravenous Administration of Microplasmin for Treatment of Acute Ischemic Stroke
• Scientific title: A Multicentre, Double-Blind, Placebo-Controlled, Ascending-dose, Clinical Trial of Intravenous Microplasmin Administration in Patients With Acute Ischemic Stroke
• Date of first enrolment: October 2005
• Target sample size: 40
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00123305
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Austria, Belgium, Germany

Contacts

• Name: Vincent Thijs, MD PhD
• Affiliation: KU Leuven

Key inclusion & exclusion criteria

Inclusion Criteria:

- Acute ischemic stroke with onset within 12 hours before randomization with baseline
NIHSS > 6 and < 22

Exclusion Criteria:

General Exclusion Criteria

- 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 time frame of the current trial

- Symptoms suggestive of subarachnoid hemorrhage, even if CT scan or MRI is negative
for hemorrhage

- Women known to be pregnant, lactating, or having a positive or indeterminate
pregnancy test

Stroke Related Exclusion Criteria

- Neurological deficit that has led to stupor or coma (National Institutes of Health
Stroke Scale [NIHSS] Level Of Consciousness Item 1a score >or=2)

- High clinical suspicion of septic embolus

- Thrombosis involving cerebral veins

- Rapidly improving neurological signs at any time before initiation of study drug
administration

Imaging Related Exclusion Criteria

- Hemorrhagic transformation or intracerebral hemorrhage observed on baseline CT of the
brain or gradient recalled echo (GRE) magnetic resonance imaging

- CT or MRI evidence of nonvascular cause for the neurological symptoms

- Large hypodensity on CT involving > 1/3 of the middle cerebral artery (MCA) territory

- Baseline DWI volume > 1/3 of the MCA territory

- Signs of mass effect causing shift of midline structures on CT or MRI

- Unable to undergo MRI (i.e., ferrous implants, cardiac pacemakers, agitation,
claustrophobia or known sensitivity to MRI contrast agents)

Safety Related Exclusion Criteria

- Congenital or acquired coagulopathy causing either of the following

1. activated partial thromboplastin time prolongation greater than 2 seconds above
the upper limit of normal (ULN) for local laboratory

2. International normalized ratio (INR) of 1.4 or more.

- 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 intravenous (IV) therapy.

- History of stroke within the previous 3 months

- Seizures at any time between stroke onset to planned initiation of study drug

- History of intracranial hemorrhage

- History of surgery, lumbar puncture, biopsy or trauma to internal organs within the
previous 30 days.

- Major trauma at the time of stroke

- Head trauma within the previous 90 days.

- Known bleeding diathesis.

- Baseline platelet count < 100 X 10^9/L.

- 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

- Life expectancy <3 months

- 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

- If treatment with tPA is indicated

- Treatment with rtPA or any other thrombolytic agent for the qualifying stroke

- Administration of intra-arterial or systemic thrombolytic therapy in previous 7 days

- Need for antiplatelet agent, unfractionated or heparin-related products, direct
thrombin inhibitor, oral anticoagulant within 24 hours after treatment bolus.

- Treatment with low molecular weight heparin, direct thrombin inhibitor, or
GPIIb/IIIa antagonists within 48 hours prior to randomisation

- Treatment with vitamin-K antagonists or heparin (or heparin-related compounds) which
results in either an INR>1.4 or an aPTT>2 times control (ULN for the hospital
laboratory)



Age minimum: 18 Years
Age maximum: 85 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Stroke, Acute

Intervention(s)

Drug: Microplasmin

Primary Outcome(s)

Intracranial haemorrhage [Time Frame: 24 hours and Day-7]

Change from Baseline in NIHSS [Time Frame: Day7 and Day-90]

Secondary Outcome(s)

Barthel Index and modified Rankin scale [Time Frame: Day-90]

Markers of systemic lysis [Time Frame: Baseline, end of treatment, 6, 12, 24, 72 and 96 hours]

Secondary ID(s)

TG-M-004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors