Study of Desmoteplase (International Nonproprietary Name [INN]) in Acute Ischemic Stroke (DIAS-2)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate desmoteplase (which is a manufactured protein derived from the saliva of the vampire bat) in dissolving clots that are blocking the flow of blood through one (or more) of the blood vessels supplying the brain, thereby reopening the blocked blood vessel and allowing blood to flow again in individuals suffering from ischemic stroke.

Official Title
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A Prospective, Randomized, Double-blind, Placebo-controlled, Single Bolus, Multinational, Multi-center, Parallel Group, Dose-ranging Study of Desmoteplase (INN) in the Indication of Acute Stroke

Conditions
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Stroke, Acute

Intervention / Treatment
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* Drug: Desmoteplase
* Drug: Desmoteplase
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for study treatment within 3-9 hours after onset of stroke symptoms. Score of 4-24 on the NIHSS with clinical signs of hemispheric infarction (i.e. hemiparesis) suggestive of ischemic stroke. Inclusion Criteria from diagnostic imaging screening: Distinct penumbra (at least 20%), measured by MRI (PWI/DWI) or perfusion CT, related to middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA) territory in a hemispheric distribution. Exclusion Criteria: History or clinical presentation of intracranial hemorrhage (ICH), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, or cerebral neoplasm. Rapidly improving neurological symptoms. Pre-stroke MRS score of > 1 (including previous disability). Suspected acute vertebral or basilar artery occlusion. Current use of anticoagulants and a prolonged prothrombin time. Uncontrolled hypertension. Baseline hematocrit of < 0.25. Baseline platelet count < 100,000/mm3.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Desmoteplase, low dose<br>Desmoteplase 90 mcg/kg, intravenous administration. | Drug: Desmoteplase<br>* Desmoteplase 90 mcg/kg, intravenous administration.<br>|
| Experimental: Desmoteplase, high dose<br>Desmoteplase 125 mcg/kg, intravenous administration. | Drug: Desmoteplase<br>* Desmoteplase 125 mcg/kg, intravenous administration.<br>|
| Placebo Comparator: Placebo<br>Dose-Match Placebo, intravenous administration. | Drug: Placebo<br>* Dose-Match Placebo, intravenous administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) | Improvement of greater than or equal to 8 points from baseline, or NIHSS score less than or equal to 1. The NIHSS score ranges from 0 (least severe) to 42 (more severe). | Change from Baseline to day 90 | 
| Modified Rankin Scale (MRS) | Improvement on the Modified Rankin Scale, defined as a score of 0-2. The MRS ranges in severity from 0 (no symptoms) to 6 (Dead). | Day 90 | 
| Barthel Index (BI) score of 75-100. | The Barthel Index (BI) is a scale used to measure performance in basic Activities of Daily Livingranges from 0 (most disablility) to 100 (no disability) | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with improvement in NIHSS score | Improvement of greater than or equal to 8 points from baseline on the NIHSS score, or NIHSS score less than or equal to 1. | From Baseline to Day 90 | 
| Percentage of patients with MRS score of 0-2 |  | Day 90 | 
| Percentage of patients with BI score of 75-100 |  | Day 90 | 
| Infarct Volume |  | Change from baseline to Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Desmoteplase, Acute Ischemic Stroke, Stroke, Acute