Abstract Details

Title The Desmoteplase DIAS-3 and DIAS-4 Clinical Trials: A Status Update

Topic Interventional Neurology

Presentation(s) P07 - (-)

Poster/Presentation
Number 249

Objective

Background BACKGROUND: rt-PA is the mainstay of thrombolysis in acute ischemic stroke (AIS), however its use has limitations. One of the current challenges is to develop a safer thrombolytic, solely targeted to the blood clot, devoid of non-fibrinolytic actions, and to be used beyond 3h after AIS. Although desmoteplase and rt-PA share 70% structural homology, their proteolytic activities differ. Desmoteplase is more fibrin specific leading to local fibrinolysis without systemic activation and fibrinogen consumption, and thus potentially a lower risk of intracerebral bleeding. In preclinical models desmoteplase, in contrast to rt-PA, is non-neurotoxic and does not increase blood-brain-barrier permeability. Based on this profile and the results of completed trials, two (N=880 in total) randomized, double-blind, placebo-controlled, phase III trials were initiated (DIAS-3 and DIAS-4) in 2009.

Design/Methods DESIGN/METHODS: The objective is to evaluate the safety/efficacy of 90 [mu]g/kg desmoteplase 3-9h after onset of AIS. Post-hoc analyses of completed trials showed that desmoteplase was favorable in patients presenting with TIMI 0-1 (occlusion or high-grade stenosis; OR 4.1), in contrast to TIMI 2-3 (OR 1.1). Therefore, patients with TIMI 0-1 (and without extended ischemic edema) are eligible to enter the trials. Primary efficacy parameter is the proportion of patients achieving modified Rankin Scale 0-2 at day 90.

Results RESULTS: The studies are progressing well. Enrollment was >50% mid-2012 and DIAS-3 is expected to finalize in 2nd half 2013. A DMC review mid-2012 revealed no safety issues and supported further recruitment.

Conclusions CONCLUSIONS: The DIAS-3 and DIAS-4 trials need our continuing support. Their results will be important for AIS patients who are in need of a safe and effective treatment.

Authors/Disclosures
Gregory W. Albers, MD (Stanford University) PRESENTER	No disclosure on file
	No disclosure on file
Jeffrey A. Cohen, MD (Cleveland Clinic)	Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Convelo. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Cohen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viatris. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PSI. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Cohen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celltrion.

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