Treatment with the novel neuroprotective agent NA-1 reduces the number of ischemic infarcts sustained by patients undergoing coiling of cerebral aneurysms, show the ENACT results.
The findings are published in The Lancet Neurology, in which the author of an accompanying commentary, Markku Kaste (Helsinki University Central Hospital, Finland), writes that "the door is now reopening for new neuroprotection trials in stroke."
Many thought the door closed after a string of high-profile failures at the phase III stage, despite several of these drugs having conformed to the Stroke Academic Industry Roundtable (STAIR) development guidelines. But NA-1 may yet prove successful because it has been shown to work in old-world primates - the closest possible animal model to humans.
Also, these failed trials were invariably in patients with acute stroke. "We needed to break the mold in order to see if success was possible," lead ENACT (Evaluating Neuroprotection in Aneurysm Coiling Therapy) investigator Michael Hill (University of Calgary, Alberta, Canada) told medwireNews.
Thus, ENACT involved 197 patients undergoing aneurysm coiling, 185 of whom ultimately received their allocated treatment: NA-1 (2.6 mg/kg) or saline delivered intravenously over 10 minutes immediately after aneurysm treatment while still under anesthesia.
The drug was given after, rather than before, the procedure because the team wished to ascertain whether NA-1 could prevent damage caused by periprocedural stroke, not whether it could prevent the stroke per se.
In the modified intention-to-treat analysis (ie, the 185 patients who actually received treatment), those given saline had an average of 7.3 new lesions on diffusion-weighted magnetic resonance imaging 12-96 hours after treatment. But patients given NA-1 had significantly fewer, at 4.1.
Lesion volumes were not different between the two groups, although when the researchers excluded two "outliers" - patients who developed major strokes several hours after the procedure - lesion volumes were significantly smaller in the NA-1 group than in the saline group (315 vs 645 mm3).
Clinical outcomes were similar between the groups, but in a prespecified analysis, patients with ruptured aneurysms appeared more likely to have good neurologic and functional outcomes if given NA-1 rather than saline. Hill suggested that this "could be due to the fact that they are sicker generally and stand to benefit more," than patients with unruptured aneurysms, but also noted that it could be a "statistical blip."
NA-1 had a good safety profile, with the team attributing no major adverse events and just two minor ones (mild transient hypotension) to the drug.
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