Dose Escalation of Desmoteplase in Acute Ischemic Stroke (DEDAS)

Study Overview
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Brief Summary
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The purpose of this study was to explore trends in safety and efficacy, and to find the optimal dose for the subsequent phase III trial. The decision to initiate the phase III trial will depend on both safety (incidence of symptomatic intracranial hemorrhage) and efficacy (reperfusion measured by MRI and correlating with clinical outcome) profiles. The safety (incidence of symptomatic intracranial haemorrhage) and efficacy (reperfusion measured by MRI and correlating with clinical outcome) profiles gained from this study were the basis of planning the phase III.

Detailed Description
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Acute stroke is the third leading cause of mortality in developed countries and the major medical cause of disability in adults. The outcome can be improved by early treatment with thrombolysis. Alteplase (r-tPA) is the only approved thrombolytic drug in the indication of acute ischemic stroke. However, the use of alteplase is currently restricted by the need to administer it within 3 hours of symptom onset. As the risk of transforming a cerebral infarct into haemorrhage probably rises as the time elapsed increases, a thrombolytic drug that carries a lower risk of haemorrhage than alteplase may offer a wider time-to-treatment window and improve the safety profile. Desmoteplase (DSPA) with its high fibrin specificity, lack of neurotoxicity, potential neuroprotective effect, non-activation by ß-amyloid, and long terminal half-life may account for an improved safety and efficacy profile within the first 9 hours after onset of symptoms.

Official Title
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International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase I/II Trial of Desmoteplase in the Indication of Acute Ischemic Stroke

Conditions
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Stroke

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: scoring 4 to 20 on the National Institute of Health Stroke Scale (NIHSS) showing a perfusion-diffusion mismatch on MRI of 20 % enrolment within a 3 h to 9 h time window after symptom onset. 18-85 years of age Exclusion Criteria: Participation in any interventional trial in the previous 30 days. Women in the childbearing age. Any history of intracranial hemorrhage, subarachnoid hemorrhage, neoplasm, arteriovenous malformation or aneurysm. Conditions that, according to the judgment of the investigator, might impose an additional risk to any individual stroke patient when receiving study medication (this applied to patients on platelet-function inhibitors as well). MRI exclusion criteria: Evidence of ICH, Evidence of SAH, Signs of extensive early infarction on DWI assessed by evidence of involvement of >1/3 of the middle cerebral artery (MCA) territory. No perfusion deficit, Internal carotid artery (ICA) occlusion ipsilateral to stroke lesion without additional ipsilateral MCA, anterior cerebral artery (ACA) or posterior cerebral artery (PCA) occlusion. Any intracranial pathology that would interfere with the MRI assessment of acute ischemic stroke.

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 |
| --- | --- |
| Active Comparator: 1<br>Desmoteplase 90µg/kg BW | Drug: Desmoteplase<br>* Desmoteplase 90µg/kg BW i.v. bolus<br>|
| Active Comparator: 2<br>Desmoteplase 125 µg/kg BW | Drug: Desmoteplase<br>* Desmoteplase 125 µg/kg BW i.v. bolus<br>|
| Placebo Comparator: 3<br>Placebo | Drug: Placebo<br>* Placebo i.v. bolus<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), Barthel-Index, mRS |  | Day 90 | 
| Reperfusion after 4-8 h |  | 8 h | 
| Infarct lesion volume after 30 days |  | Day 30 | 
| Safety & pharmacokinetic outcomes |  | Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke