番茄社区

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LOS ANGELES -- An ambitious trial to test a novel approach to treat intraventricular hemorrhage failed its primary endpoint, which was a measure of disability, but it did produce a "strong biologic signal" suggesting the treatment can save lives and reduce overall disability.

Nonetheless, disappointment with the results was palpable as , of Johns Hopkins University, told a press conference at the International Stroke Conference here, "The fact is we failed and we cannot reject that null hypothesis."

But he and his colleagues learned important lessons that will, he said, direct future efforts: the larger the clot, the better the outcome -- and most importantly, success depends on the amount of clot that is evacuated with the threshold for benefit being about 85% of the clot and "major benefit seen when 90% is evacuated."

For 10 years, Hanley has championed what seems like a counterintuitive approach: using a lytic drug to treat the aftermath of a hemorrhagic stroke and he had high hopes for a trial called or Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage.

The basic concept is that recovery from these devastating strokes requires rapid evacuation of blood that pools and eventually clots in the ventricles after the initial bleeding stops. One approach used by neurosurgeons is to insert an endovascular drain in the hope that it would relieve pressure by draining intracerebral fluid and possibly help the blood to drain away. But Hanley said that process was slowed as the blood clotted around the drain and impeded the process.

By introducing alteplase, Hanley theorized that the blood could flow freely thus rapidly evacuating the clot.

He and his colleagues enrolled 500 patients with severe intravascular hemorrhage with small intracranial hemorrhage (ICH). He told 番茄社区 that this stroke subtype has a high mortality rate -- 50% -- and 80% of survivors have a poor outcome with permanent disability. The patients were randomized to low dose alteplase, 1 mg every 8 hours for a maximum of 12 doses, or to saline delivered by catheter.

The primary endpoint was functional improvement as measured by the modified Rankin stroke scale, which was assessed at 30, 180 and 365 days. At 180 days, that measure failed to show significant improvement for the drug versus placebo.

Other outcome measures, including the Glasgow Outcome Scale that comprises hard endpoints such as mortality and vegetative state, did suggest a benefit: a 10% reduction in mortality and a reduction in bacterial infections, probably because the clot was evacuated more quickly. By that measure, treating just 10 patients would prevent a death or major disability.

"But that was not the measure we chose," Hanley said.

Neurosurgeon , of the University of Chicago and a co-investigator for CLEAR III, said the most important takeaway was the finding that the catheter needs to be placed in the clot to achieve maximum benefit. Neurosurgeons traditionally have been wary of placing a catheter directly in the clot, but the study provided evidence that this critical placement could increase the amount of blood that is drawn off, thus improving functional outcomes.

Hanley said that he is planning CLEAR IV but noted that he has not yet secured funding for such a trial.

From the American Heart Association: