|Volume 6 Issue 40 Published - 14:00 UTC 08:00 EST 9-Feb-2004 Next Update - 14:00 UTC 08:00 EST 10-Feb-2004||Editor: Susan K. Boyer, RN
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Desmoteplase in stroke: Successful phase II results
The DIAS and DEDAS Studies
The DIAS study (Desmoteplase In Acute Ischemic Stroke) was a multicentre, placebo-controlled, randomized dose finding Phase II study. 25 hospitals from Europe, Australia and Asia recruited a total of 102 patients. Patients were included in the time window between three and nine hours after the onset of stroke symptoms. A sister study DEDAS ("Dose Escalation study of Desmoteplase in Acute Ischemic Stroke") is ongoing in 17 centers in the US with the same study design. In both studies MRI was used to identify patients who have the potential to benefit most from reperfusion therapy.
Desmoteplase and Stroke
Desmoteplase is a genetically engineered version of a blood clot-dissolving protein from the saliva of the vampire bat Desmodus rotundus. Desmoteplase acts in a similar way as rt-PA, but is almost exclusively activated through fibrin. As a result of this "selective lysis" Desmoteplase is able to dissolve the blood clot locally without affecting the integrity of the body's blood coagulation system, which is thought to reduce the risk of intracranial bleeding as compared to less fibrin specific plasminogen activators. Recent data show that Desmoteplase has also neuroprotective properties, which are distinct from rt-PA.
The analysis of the second part of the DIAS (Desmoteplase In Acute Ischemic Stroke) study has met the high expectations for the substance Desmoteplase, which is already known as the "Vampire Bat Plasminogen Activator".
Dose dependent reperfusion
By administering Desmoteplase the blood flow in the damaged brain area of patients was significantly improved and expansion of the damaged brain area was prevented. This re-established perfusion (reperfusion), measured by magnetic resonance imaging (MRI) was dependant on the dose administered and could be achieved in 46.7 % of patients with a dose of 90µg/kg Desmoteplase whereas the highest well tolerated dose of 125µg/kg led to reperfusion in even 71.4% of patients.
Reperfusion translating into clinical improvement Better reperfusion translated into better clinical outcome, measured with a combined endpoint consisting of the NIH Stroke Scale, modified Rankin Scale (mRS) and Barthel Index (BI). With the dose of 90µg/kg 46.7 % and with 125µg/kg 60% of patients reached the pre-defined clinical endpoint at 90 days after treatment.
Safety in the late time window A known side effect of thrombolysis is intra-cranial bleeding. Based on earlier results, new dosages were tested and showed a positive safety profile, clearly exceeding the expectations for the drug, when administering 90 µg/kg or 125 µg/kg. The combined rate of intra-cranial bleeding for both groups was 3.3 % and bleeding risk was not higher for patients treated 6 to 9 hours after the acute event as compared to those treated between 3 to 6 hours.
"The study emphasises that by using new diagnostic techniques, an effective and safe reperfusion could be possible in a longer time window. I hope that in the future more centres will use this technique", says Professor Werner Hacke, Director of the Neurological University Clinic of Heidelberg in Germany and principal investigator of the completed DIAS study.
Anthony Furlan, Medical Director of the Cerebrovascular Center, Cleveland Clinic Foundation, Ohio, and principal investigator of PAION's ongoing US trial (DEDAS) is very encouraged by these results: "We are now even more eager to complete the US trial with Desmoteplase in the hope that we will replicate the impressive safety and improvement in outcomes seen in DIAS. The results of the DIAS trial have reinvigorated interest in reperfusion with a plasminogen activator beyond 3 hours in the US and the world stroke community."