Desmoteplase in Acute Ischemic Stroke (DIAS)
Primary Purpose
Stroke
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Desmoteplase
Desmoteplase
Desmoteplase
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Stroke focused on measuring Acute ischemic stroke
Eligibility Criteria
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.
Sites / Locations
- Prof. Dr. Werner Hacke
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
1
2
3
4
Arm Description
Desmoteplase 62.5 µg/kg BW i.v. bolus
Desmoteplase 90 µg/kg BW i.v. bolus
Desmoteplase 125 µg/kg BW i.v. bolus
Placebo i.v. bolus
Outcomes
Primary Outcome Measures
National Institutes of Health Stroke Scale (NIHSS), Barthel-Index & mRS
Change in lesion volume
Secondary Outcome Measures
Reperfusion after 4-8 h
Safety and pharmacoeconomic outcomes
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00638781
Brief Title
Desmoteplase in Acute Ischemic Stroke (DIAS)
Official Title
Multicentre, Multinational, Double-Blind, Placebo-Controlled, Randomised Phase II Trial of Desmoteplase (INN) in the Indication of Acute Ischaemic Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
March 2008
Overall Recruitment Status
Completed
Study Start Date
March 2001 (undefined)
Primary Completion Date
October 2003 (Actual)
Study Completion Date
October 2003 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
PAION Deutschland GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The DIAS study (Part 2) was performed to support the dose finding of desmoteplase treatment in subjects with acute ischemic stroke selected by perfusion/diffusion mismatch on MRI within a time window of 3 to 9 h after stroke-symptom onset. In addition, it assessed safety and tolerability of 3 doses of desmoteplase compared with placebo with special consideration of intracranial hemorrhage and major systemic bleedings.
Detailed Description
Acute stroke is the third leading cause of mortality in developed countries and the major medical cause of disability. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Acute ischemic stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
104 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Desmoteplase 62.5 µg/kg BW i.v. bolus
Arm Title
2
Arm Type
Active Comparator
Arm Description
Desmoteplase 90 µg/kg BW i.v. bolus
Arm Title
3
Arm Type
Active Comparator
Arm Description
Desmoteplase 125 µg/kg BW i.v. bolus
Arm Title
4
Arm Type
Placebo Comparator
Arm Description
Placebo i.v. bolus
Intervention Type
Drug
Intervention Name(s)
Desmoteplase
Intervention Description
Desmoteplase 62.5 µg/kg BW
Intervention Type
Drug
Intervention Name(s)
Desmoteplase
Intervention Description
Desmoteplase 90 µg/kg BW
Intervention Type
Drug
Intervention Name(s)
Desmoteplase
Intervention Description
Desmoteplase 125 µg/kg BW
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
National Institutes of Health Stroke Scale (NIHSS), Barthel-Index & mRS
Time Frame
Day 90
Title
Change in lesion volume
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
Reperfusion after 4-8 h
Time Frame
8 h
Title
Safety and pharmacoeconomic outcomes
Time Frame
Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Werner Hacke, Prof. Dr.
Organizational Affiliation
Head of Neurology Department, University of Heidelberg
Official's Role
Study Chair
Facility Information:
Facility Name
Prof. Dr. Werner Hacke
City
Heidelberg
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
15569863
Citation
Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S; DIAS Study Group. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005 Jan;36(1):66-73. doi: 10.1161/01.STR.0000149938.08731.2c. Epub 2004 Nov 29.
Results Reference
result
PubMed Identifier
22738918
Citation
Warach S, Al-Rawi Y, Furlan AJ, Fiebach JB, Wintermark M, Lindsten A, Smyej J, Bharucha DB, Pedraza S, Rowley HA. Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials. Stroke. 2012 Sep;43(9):2313-8. doi: 10.1161/STROKEAHA.111.642348. Epub 2012 Jun 26.
Results Reference
derived
PubMed Identifier
22474060
Citation
Fiebach JB, Al-Rawi Y, Wintermark M, Furlan AJ, Rowley HA, Lindsten A, Smyej J, Eng P, Warach S, Pedraza S. Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke. 2012 Jun;43(6):1561-6. doi: 10.1161/STROKEAHA.111.642322. Epub 2012 Apr 3.
Results Reference
derived
Links:
URL
http://www.paion.de
Description
PAION Deutschland GmbH
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Desmoteplase in Acute Ischemic Stroke (DIAS)
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