Desmoteplase safely restored blood flow to brain up to nine hours after stroke onset

Experimental thrombolytic drug extended treatment period, improved clinical outcome after ischemic stroke.

Desmoteplase, a clot-reducing drug derived from the saliva of vampire bats, improved brain reperfusion in patients who had suffered an ischemic stroke in the DEDAS trial. The drug also prolonged the amount of time to effectively treat strokes by up to six hours. The only FDA-approved clot-reducing drug available now should be administered within three hours of stroke onset.

“The main finding of [DEDAS] was that no symptomatic brain hemorrhages occurred with either dose, and there were no excess serious adverse events, including mortality, in desmoteplase patients,” Anthony Furlan, MD, head of the section of stroke and neurologic intensive care and medical director of the Cerebrovascular Center at the Cleveland Clinic, told Cardiology Today.

Furlan, who presented the results at the American Stroke Association International Stroke Conference 2005, said the study was conducted “to see if we could confirm the results of the Desmoteplase in Acute Stroke (DIAS) study and to further explore the safety and efficacy of desmoteplase in patients with ischemic stroke of three to 9 hours duration.”

The DIAS trial, reported at last year’s meeting, showed the drug’s success with expanding the time window for treatment and demonstrated that new MRI techniques were key in helping to select the right patients for therapy.

Higher dose more effective

The DEDAS trial (Dose Escalation study of Desmoteplase in Acute Ischemic Stroke) was a dose escalation, phase II study performed in the United States and Germany. Thirty-eight patients, aged 18 to 85, were randomized to intravenous desmoteplase doses of either 90 µg/kg (low dose) or 125 µg/kg (high dose), or to a placebo in a dose escalating manner with a 15:4 randomization ratio (active: placebo) per dose tier within three to nine hours after stroke onset.

All patients had scored between four and 20 on the National Institute of Health Stroke Scale.

Within eight hours of treatment, reperfusion occurred in 53.3% of the patients who received a high dose of desmoteplase (Paion GmbH, Aachen, Germany), 18.2% of the patients who received a low dose and 37.5% of the patients who received a placebo.

None of the patients developed symptomatic intracerebral hemorrhage and the mortality rate remained unchanged.

Evaluation by MRI

Ninety days after the doses of desmoteplase were administered, improved clinical outcomes were also recorded. Sixty percent of patients who received the high dose were well enough to perform normal daily activities on their own. Only 28.6% of the low-dose patients and 25% of placebo patients experienced the same result.

“We saw a strong efficacy signal with 125 µg/kg desmoteplase dose compared to placebo in two ways,” Furlan said. “First, brain reperfusion on MRI four to eight hours after treatment was better in treated patients compared to placebo.

“Second, reperfusion was associated with statistically significant better clinical outcomes at 90 days,” Furlan said. – by Nancie Brown

For more information:

• Furlan A. Results of the dose escalation study of desmoteplase in acute ischemic stroke (DEDAS). Presented at the American Stroke Association International Stroke Conference 2005. Feb. 2-4, 2005. New Orleans.