A global clinical trial has found that a drug, designed to rapidly slow bleeding in the brain after a hemorrhagic stroke, does not improve long‑term recovery for patients, according to a study published in The Lancet.
The trial, conducted across 93 hospitals in six countries, tested whether giving recombinant factor VIIa within two hours of a spontaneous intracerebral hemorrhage (ICH) could improve patient outcomes after 180 days.
Despite measurable biological effects, investigators found no improvement in functional recovery, compared to a placebo.
“We were able to reduce bleeding, but that wasn’t enough to improve patients’ long‑term outcomes,” said Andrew M. Naidech, MD, MSPH, professor in the Ken & Ruth Davee Department of Neurology, Division of Neurocritical Care, who was a co-author of the study. “It reinforces that stopping the hemorrhage is only one piece of a much more complex problem.”
More than 600 patients participated in the study and were randomly assigned to receive either recombinant factor VIIa or an identical placebo. All doses were delivered within two hours of symptom onset — one of the earliest treatment windows attempted in ICH research.
The modified Rankin Scale, the gold-standard measure of stroke disability, showed no outcome difference between groups at 180 days.
Although functional outcomes did not improve, imaging showed that recombinant factor VIIa significantly slowed the growth of both intracerebral and intraventricular hemorrhages.
Still, the treatment carried risks. Life-threatening thromboembolic events occurred in 15 patients in the treatment group, compared with four on placebo.
“Any medication that enhances clotting will carry a thrombotic risk,” Naidech said. “What we still need to determine is whether there’s a subgroup where the bleeding risk is so high that the potential benefit outweighs that danger.”
Several factors may explain why the drug’s biological effect did not translate into better recovery, Naidech said. Brain damage from ICH often occurs within minutes, before treatment is possible and hematoma location can be more important than size. Additionally, preventing secondary injury — swelling, inflammation, tissue toxicity — requires therapies beyond clotting control.
“ICH is not just about the volume of blood,” Naidech said. “It’s about where that blood is, how the brain responds, and how quickly irreversible injury develops.”
While the trial did not show a broad clinical benefit, Naidech said the drug may still help a narrower group of patients.
“We believe there are patients with extremely rapid, ongoing bleeding who could still benefit,” he said. “That’s where research is headed next.”
The trial was funded by the National Institute of Neurological Disorders and Stroke, the Japan Agency for Medical Research and Development, and Novo Nordisk, the manufacturer of recombinant factor VIIa.
