It Takes Trial and Error to Reach Discovery
Major Stroke Trial’s Findings Underscore the Importance of Perseverance and Adaptation in Clinical Research
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Clinical trials are less about certainty than discovery—sometimes substantiating a hypothesis, sometimes proving it wrong, and at times landing somewhere in between. Such was the case with the results of a recent clinical trial published in The Lancet by an international group of investigators, including Stephan Mayer, M.D., professor of neurosurgery and of neurology at New York Medical College, that examined the use of recombinant factor VIIa (rfVIIa), which stimulates blood coagulation, to treat intracerebral hemorrhage (ICH). Despite advances, ICH remains the most devastating type of stroke, with nearly half of patients dying within 30 days and only 20 percent functionally independent after six months.
This latest trial follows up on a concept developed by Dr. Mayer that led to two trials published in the New England Journal of Medicine more than 10 years ago. “We know that the greater the amount of intracerebral bleeding, the greater the risk of death and disability from ICH, with most of that bleeding taking place in the first two or three hours after symptoms occur,” says Dr. Mayer. “With ischemic stroke, when a clot clogs an artery, we give a clot-busting drug to dissolve the clot, so why not use a drug like rfVIIa to form a clot to stop intracerebral bleeding?”
While the initial trial in 2005 yielded promising results, a second, larger trial in 2008 failed to show an improvement in functional outcomes for patients treated with rfVIIa within four hours of the onset of symptoms, leading the drug manufacturer to cancel the testing program. Then, in 2018, Dr. Mayer was approached by Joseph Broderick, M.D., a prominent stroke expert, to propose testing rfVIIa for ICH patients again, using an even smaller treatment window of just two hours from symptoms to treatment injection.
“What seemed crazy fast in 2008 is just standard practice today,” says Dr. Mayer. “We now routinely give IV thrombolytics within 20 to 25 minutes of a patient hitting the door. That used to be viewed as impossible, but stroke systems of care are much stronger, public education has improved, and stroke teams are more focused and coordinated. Door-to-needle time is now a widely accepted quality metric.”
The “FASTEST“ trial enrolled 626 participants across 93 sites in six countries between December 2021 and October 2025, with Dr. Mayer serving on the executive committee and as the independent medical safety monitor.
Though the trial once again demonstrated less bleeding in hemorrhage growth, even the more rapid treatment window couldn't move the clinical outcomes, and given the inherent thrombotic risks, the trial was discontinued after an interim analysis of the data. But the study was not without some positive results. Patients with a "spot sign" on CT angiography (the presence of extravasated blood within a hematoma) and those treated within 90 minutes showed a greater reduction in bleeding and signs of an improved clinical outcome.
“The upshot is that our efforts are continuing,” says Dr. Mayer. “We know rfVIIa does what it's supposed to do. It's now a matter of trying to show we can identify a patient group reliably, where it's clearly, unequivocally helping them make better recoveries or suffer less severe strokes.”
To illustrate, Dr. Mayer points to Dr. Broderick’s first study of mechanical thrombectomy for ischemic stroke, which didn’t appear to be effective, until subsequent studies demonstrated its success when treating patients shown to have a large clogged artery on a CT angiogram.
“So, a lot in trials is patient selection,” he continues. “It's normal to experience failure in trials, especially when you're pioneering, but you can always learn from that and refine your techniques and your approach, and then hopefully at some point you'll hit it.”
