Dose Escalation of Desmoteplase in Acute Ischemic Stroke (DEDAS) - Full Text View

Sponsored by:	PAION Deutschland GmbH
Information provided by:	PAION Deutschland GmbH
ClinicalTrials.gov Identifier:	NCT00638248

Purpose

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.

Condition	Intervention	Phase
Stroke	Drug: Desmoteplase Drug: Placebo	Phase I Phase II

Drug Information available for: Desmoteplase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase I/II Trial of Desmoteplase in the Indication of Acute Ischemic Stroke

Further study details as provided by PAION Deutschland GmbH:

Primary Outcome Measures:

National Institutes of Health Stroke Scale (NIHSS), Barthel-Index, mRS [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
Reperfusion after 4-8 h [ Time Frame: 8 h ] [ Designated as safety issue: No ]
Infarct lesion volume after 30 days [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
Safety & pharmacokinetic outcomes [ Time Frame: Day 90 ] [ Designated as safety issue: No ]

Enrollment:	38
Study Start Date:	March 2003
Study Completion Date:	October 2004
Primary Completion Date:	October 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Desmoteplase 90µg/kg BW	Drug: Desmoteplase Desmoteplase 90µg/kg BW i.v. bolus
2: Active Comparator Desmoteplase 125 µg/kg BW	Drug: Desmoteplase Desmoteplase 125 µg/kg BW i.v. bolus
3: Placebo Comparator Placebo	Drug: Placebo Placebo i.v. bolus

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638248

Sponsors and Collaborators

PAION Deutschland GmbH

Investigators

Principal Investigator:

Antony J. Furlan, MD

Department of Neurology; the Cleveland Clinic Foundation

More Information

Study Publication This link exits the ClinicalTrials.gov site

PAION Deutschland GmbH This link exits the ClinicalTrials.gov site

Publications of Results:

Furlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA, Sachara C, Soehngen M, Warach S, Hacke W; DEDAS Investigators. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006 May;37(5):1227-31. Epub 2006 Mar 30.

Responsible Party:	PAION Deutschland GmbH ( Karin Wilhelm-Ogunbiyi, MD / Medical Director & Head of Clinical Development )
Study ID Numbers:	PN01-CLD-000002/01
Study First Received:	March 12, 2008
Last Updated:	March 12, 2008
ClinicalTrials.gov Identifier:	NCT00638248
Health Authority:	United States: Food and Drug Administration; Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by PAION Deutschland GmbH:

Acute ischemic stroke

Study placed in the following topic categories:

Cerebral Infarction
Stroke
Vascular Diseases
Brain Ischemia
Central Nervous System Diseases
Brain Infarction

Ischemia
Brain Diseases
Infarction
Plasminogen
Salivary plasminogen activator alpha 1, Desmodus rotundus
Cerebrovascular Disorders

Additional relevant MeSH terms:

Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Hematologic Agents
Nervous System Diseases

Fibrinolytic Agents
Cardiovascular Diseases
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009