Results from the largest-ever clinical trial of its kind found administering a synthetic protein can reduce bleeding and improve outcomes for certain patients at the highest risk of continued bleeding following a type of stroke called an intracerebral hemorrhage (ICH).
The University of Cincinnati's Joseph Broderick, MD, presented results from the FASTEST trial at the International Stroke Conference on Feb. 4. Findings were additionally published in The Lancet, with Broderick serving as corresponding author.
An ICH occurs when a blood vessel bursts inside the brain and causes bleeding in the brain. ICHs account for approximately 15% of all strokes but a disproportionate 50% of all stroke deaths.
The international Phase 3 FASTEST trial tested a drug called recombinant factor VIIa (rFVIIa), a synthetic version of a protein the body naturally produces to help stop bleeding.
Across 93 sites in the United States, Canada, Germany, Japan, Spain and the United Kingdom, 328 patients were randomized to receive the study drug and 298 were randomized to the placebo arm. All patients were given the drug or placebo within two hours of stroke onset.
Overall findings of the trial were neutral, and the trial was ended early for futility. While the drug did slow bleeding overall, there was a lack of evidence of benefit for clinical outcomes in the overall study population.
However, researchers found the drug was most effective in people who have what is called a "spot sign" on computed tomography (CT) brain imaging and for patients treated within 90 minutes of stroke onset.
"A spot sign depicts leakage of contrast dye from the ruptured vessel," said Broderick, professor in UC's College of Medicine, senior adviser at the UC Gardner Neuroscience Institute and director of the NIH StrokeNet National Coordinating Center. "The amount the drug slows bleeding is accompanied by signals for potential benefit in these two subgroups."
Patients with a spot sign and those treated within 90 minutes who received rFVIIa were found to have better outcomes 90 days after an ICH.
These patients also had a substantially greater decrease in moderate or severe ICH growth. In fact, Broderick said this was the largest reduction of ICH growth ever observed in a trial testing treatments for spontaneous ICH.
Moving forward, the next phase of the trial will continue to test rFVIIa in patients with spot signs and in those who are able to be treated within 90 minutes. Broderick noted researchers are working to deliver the treatment as close to initial stroke onset as possible.
"The closer to time zero you can treat, the less bleeding you are likely to have with rFVIIa treatment," he said. "It makes biological and clinical sense, which is why we're doing FASTEST Part 2 in these subgroups."
