Intravenous Administration of Microplasmin for Treatment of Acute Ischemic Stroke

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00123305
Recruitment Status : Completed
First Posted : July 22, 2005
Last Update Posted : November 7, 2014
Information provided by (Responsible Party):

Brief Summary:
The primary purpose of this study is to evaluate the safety and preliminary efficacy of microplasmin when administered intravenously to patients who have suffered an acute stroke within 12 hours before randomization.

Condition or disease Intervention/treatment Phase
Stroke, Acute Drug: Microplasmin Phase 2

Detailed Description:

While the primary objective of the trial is safety evaluation, efficacy assessments will also be obtained, including MRI/MRA (including DWI, PWI and T2 imaging) and plasma surrogate biomarkers. Clinical outcome will also be assessed at 7days, 30 days and 90 days post-treatment. At each of these visits, mortality and neurological assessments (NIHSS, Barthel index, mRankin scale) will be performed. In addition, vital status will be assessed vial a telephone contact at 60 days post-treatment.

The trial will investigate three dose regimens of microplasmin, all of which are within the range of doses previously evaluated in a Phase I trial in healthy volunteers; the planned sample size for the trial is approximately 40 patients.

The study will consist of 3 phases - the Baseline, In-hospital Phase and Follow up Phase. Baseline is from study entry through randomisation; the In-hospital phase is from treatment with study drug through hospital discharge or day 7, whichever occurs first. The follow up phase consists of visits to the hospital 30 days (+ 3 days) from the day of study drug administration. Hospital discharge is defined as the end of the discharge from the acute hospital setting. Discharge may be to home, to a rehabilitation setting or to a non-acute hospital setting.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicentre, Double-Blind, Placebo-Controlled, Ascending-dose, Clinical Trial of Intravenous Microplasmin Administration in Patients With Acute Ischemic Stroke
Study Start Date : October 2005
Actual Primary Completion Date : May 2008
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Ocriplasmin
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1 Drug: Microplasmin
1mg/kg bolus of microplasmin solution followed by 1,2 or 3mg/kg infusion of mircroplasmin solution.
Experimental: 2 Drug: Microplasmin
1mg/kg bolus of microplasmin solution followed by 1,2 or 3mg/kg infusion of mircroplasmin solution.
Experimental: 3 Drug: Microplasmin
1mg/kg bolus of microplasmin solution followed by 1,2 or 3mg/kg infusion of mircroplasmin solution.
Placebo Comparator: 4 Drug: Microplasmin
1mg/kg bolus of placebo solution followed by 1,2 or 3mg/kg infusion of placebo solution

Primary Outcome Measures :
  1. Intracranial haemorrhage [ Time Frame: 24 hours and Day-7 ]
  2. Change from Baseline in NIHSS [ Time Frame: Day7 and Day-90 ]

Secondary Outcome Measures :
  1. Barthel Index and modified Rankin scale [ Time Frame: Day-90 ]
  2. Markers of systemic lysis [ Time Frame: Baseline, end of treatment, 6, 12, 24, 72 and 96 hours ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00123305

Universitatsklinik fur Neurologie
Graz, Austria, 8036
Landesnervenklinik Wagner-Jauregg
Linz, Austria, 4020
AKH Linz Neurolog Abt
Linz, Austria, A-4020
Allgemeines Offentliches Krankenhaus der
Linz, Austria, A-4021
Cliniques Universitaires St Luc
Brussels, Belgium, 1200
Gasthuisburg Hospital
Leuven, Belgium, B-3000
Universitätsklinikum Erlangen
Erlangen, Germany, 91054
Universitatsklinikum Essen
Essen, Germany, 45122
Klinikum der J.W Goethe Univeristy
Frankfurt, Germany, 60528
Universitatsklinikum Freiburg
Freiburg, Germany, 79106
Georg August Universitat Gottingen
Gottingen, Germany, 37075
Universitatskrankenhaus Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitatsklinikum Leipzig
Leipzig, Germany, 04103
Klinikum Minden, Chefarzt der Neurologischen Klinik
Minden, Germany, 32427
Klinikum rechts der Isar der TU München
München, Germany, 81675
HSK Dr. Horst Schmidt Hospital
Wiesbaden, Germany, 65199
Sponsors and Collaborators
Principal Investigator: Vincent Thijs, MD PhD KU Leuven

Responsible Party: ThromboGenics Identifier: NCT00123305     History of Changes
Other Study ID Numbers: TG-M-004
First Posted: July 22, 2005    Key Record Dates
Last Update Posted: November 7, 2014
Last Verified: November 2014

Keywords provided by ThromboGenics:
Acute Ischemic Stroke

Additional relevant MeSH terms:
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action