Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4)

Study Overview
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Brief Summary
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The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

Detailed Description
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Acute stroke is a major cause of mortality and long-term disability in the developed world. The only currently approved thrombolytic intervention for acute ischemic stroke, which constitutes the majority of strokes, is alteplase (recombinant tissue plasminogen activator; rtPA). The use of alteplase is limited as it is approved for use within 3 hours after symptom onset and by the risk of inducing intracerebral haemorrhage; consequently fewer than 3% of acute stroke subjects are treated. The thrombolytic agent desmoteplase (recombinant Desmodus Salivary Plasminogen Activator alpha-1; rDSPAalpha-1) produced by recombinant biotechnology has its naturally occurring counterpart in the saliva of the vampire bat Desmodus rotundus. Compared to alteplase, desmoteplase has a more favourable profile in terms of high fibrin specificity and non neurotoxicity. The study aims to confirm efficacy and safety of desmoteplase for thrombolytic therapy of patients with acute ischaemic stroke in the extended time window of 3 to 9 hours after onset of stroke symptoms.

Official Title
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A Randomised, Double-Blind, Parallel-Group Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Desmoteplase in Subjects With Acute Ischemic Stroke

Conditions
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Stroke

Intervention / Treatment
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* Drug: Desmoteplase
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute ischemic stroke Informed consent Age between 18 and 85 years Treatment can be initiated within 3 to 9 hours after the onset of stroke symptoms NIHSS Score of 4 to 24 Vessel occlusion or high-grade stenosis on MRI or CTA in proximal cerebral arteries Exclusion Criteria: Pre-stroke mRS >1 Previous exposure to desmoteplase Extensive early infarction on MRI or CT in any affected area Imaging evidence of ICH or SAH; AV malformation; cerebral aneurysm; or cerebral neoplasm Internal carotid artery occlusion on the side of the stroke lesion Treatment with heparin in the past 48 hours and a prolonged partial thromboplastin time Treatment with oral anticoagulants and a prolonged prothrombin time Treatment with glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors is permitted Treatment with a thrombolytic agent within the past 72 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desmoteplase<br> | Drug: Desmoteplase<br>* 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes on 1st day<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* IV, single bolus over 1 to 2 minutes on 1st day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2) | The mRS is a clinician-rated scale designed to provide a global assessment of the patients dependency after stroke. The scale consists of a single item measuring the patient's function based on the ability to perform daily activities. The patient is rated on a 7-point scale from 0 to 6, where a score of 5 corresponds to severe disability, and 6 to death. Assessment of a pre-stroke mRS score is based on an interview addressing the status of the patient prior to the stroke | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8) | The NIHSS is a clinician-rated, 15-item scale designed to assess the severity of stroke-related neurological deficits: level of consciousness, eye movements, visual fields, facial symmetry, motor strength (arm and leg), coordination, sensation, language (aphasia and dysarthria), and neglect. Each item is rated on a 3-, 4-, or 5-point scale ranging from 0 (normal) to the maximum score (extremely severe symptoms). The total score of the 15 items ranges from 0 to 42, where lower scores indicate less impairment. | 90 days | 
| Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8) | Please see outcomes measure one and two for detailed description of the scales | Day 90 | 
| Modified Ranking Scale Score (Using the Ordinal Scale) | Please see outcomes measure one for detailed description of the mRS scale | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Angiography, Desmoteplase, Thrombolytic