Desmoteplase didn't help late-presenting strokes, the DIAS-3 trial shows.
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A good functionally independent outcome, marked by a modified Rankin Scale score of 0 to 2, at 90 days occurred in 51% of desmoteplase-treated patients compared with 50% given placebo (P=0.40), Gregory W. Albers, MD, of the Stanford School of Medicine in Stanford, Calif., and colleagues found.
Recanalization at 24 hours, monitored with noninvasive imaging, likewise came out similar between treatment groups (49% and 42%, respectively), they reported in the June issue of Lancet Neurology.
"This factor is key in the neutral results and raises questions about the thrombolytic efficiency of desmoteplase in late time windows," Michael D. Hill, MD, and Bijoy K. Menon, MD, both of the University of Calgary Stroke Program in Alberta, wrote in an accompanying editorial.
However, imaging protocol violations were common in the trial, with imaging discrepancies in 21% of the 292 acute ischemic stroke patients with occlusion or high-grade stenosis in major cerebral arteries treated at a median 7 hours after onset.
Although serious adverse events, including intracerebral hemorrhage and symptomatic cerebral edema, were similar between groups, another phase III trial, DIAS-4, was stopped based on early indications of futility in DIAS-3.
The researchers pointed to a possible benefit of desmoteplase in small ischemic lesions selected by MRI that might be worth further study.
While that group might have been less prone to imaging measurement error, "this finding would have been more meaningful if increased recanalization early after administration of the thrombolytic agent was also shown in the small core group," the editorialists cautioned.
It may be that late-presenting, small core strokes are just not a good population to target, they suggested.
"We speculate that patients who arrive late without having a large, established core of infarction shown in imaging are more likely to have preserved penumbral tissue because of good intracranial collateral circulation," Hill and Menon wrote. "Such patients could stand to benefit less from thrombolysis, even with reperfusion.
"Further, with time, thrombi mature and fibrin cross-links, resulting in resistance to thrombolysis. Patients who present in later time windows might simply be less amenable to chemical thrombolysis."