NEW ORLEANS — A new trial of recombinant factor VIIa in patients with intracerebral hemorrhage (ICH) showed neutral overall results but raised the possibility that the therapy could help stop bleeding and improve outcomes in selected patients.

Results of the FASTEST trial showed that administering recombinant factor VIIa within 2 hours of ICH onset slowed hematoma growth but did not improve functional outcomes in the overall study population and was associated with a small increase in life-threatening thromboembolic complications.

However, subgroup analyses suggested that the biological effect of slowing bleeding was largely concentrated in two patient groups: those with a spot sign on CT angiography, a marker of ongoing bleeding, and those treated within 90 minutes of symptom onset. 

In these subgroups, treatment with factor VIIa was associated with signals suggesting clinical benefit. Building on these findings, a new trial, FASTEST-2, is now underway, enrolling patients with ICH treated within 90 minutes of onset or those with a positive spot sign within 120 minutes.

“These two subgroups are where we seem to be able to make a difference. These patients are the ones most likely to still be actively bleeding so it makes sense that giving an agent to stop bleeding would work here,” lead investigator, Joseph Broderick, MD, medical director of the UC Gardner Neuroscience Institute at the University of Cincinnati, Cincinnati, told Medscape Medical News.

“These subgroup results look very promising, and if the FASTEST-2 trial confirms these findings, this would be the first medical treatment for ICH. This is a catastrophic event and there is very little we can do for these patients at present apart from controlling blood pressure. These results suggest that we could have a treatment for selected patients in the not-too-distant future,” he added.

Broderick presented the results of the FASTEST trial on February 4 at the International Stroke Conference (ISC) 2026. The study was also simultaneously published online in The Lancet.

Largest Trial of Hyperacute Stroke

Factor VIIa is a naturally occurring protein involved in blood clot formation and vessel repair. In ICH, the therapeutic goal is to seal a ruptured blood vessel that is actively bleeding in the brain. Most hematoma expansion occurs within the first 2-3 hours after symptom onset, and earlier studies may not have treated patients quickly enough, Broderick noted.

The FASTEST trial was designed to intervene more rapidly and to focus on patients most likely to benefit, excluding very older individuals and those with extremely large hemorrhages who are unlikely to have good outcomes even if bleeding is controlled, Broderick explained.

The study was the largest hyperacute stroke trial to require brain imaging before treatment and was conducted at 93 sites in the US, Japan, Canada, Spain, Germany, and the UK.

The trial included 626 patients (mean age, 61 years) with spontaneous ICH volumes of 2-60 mL and limited intraventricular hemorrhage (IVH), defined as involvement of less than two thirds of one lateral ventricle or less than one third of both lateral ventricles, who presented within 2 hours of symptom onset.

Eligible patients were also required to have a Glasgow Coma Scale score of ≥ 8 and no evidence of a recent ischemic stroke or myocardial infarction, recent use of anticoagulation therapy, or another structural cause of ICH.

To facilitate rapid enrollment, the trial used mobile stroke units and waived emergency consent requirements. Patients were randomized to receive factor VIIa (80 μg/kg) or placebo, administered intravenously over 2 minutes.

The primary outcome was functional outcome at 180 days, measured by modified Rankin Scale (mRS) score. The secondary aim was the change in ICH volume and ICH plus IVH volume between baseline and 24 hours of treatment administration.

The trial was stopped for futility at the second interim analysis, with results showing no significant difference in the primary clinical outcome measure of mRS change at 180 days between the intervention group and the placebo group (adjusted common odds ratio [OR], 1.09 [95% CI, 0.79-1.51]; P = .61).

Life-threatening thromboembolic complications within 4 days occurred in 15 participants (< 5%) in the intervention group and in four (1%) in the placebo group (relative risk, 3.41; P = .02).

Compared with placebo, recombinant factor VIIa was associated with decreased growth of ICH (-3.7 mL) and of ICH plus IVH (-5.2 mL) between baseline and CT scan at 24 hours.

Potential Benefit in Two Subgroups

Among the 511 patients who had a baseline CT angiography either before or after study drug administration, 29% had a spot sign. In this group, patients who received factor VIIa showed a greater chance of a favorable clinical outcome on the mRS scale (adjusted common OR, 1.86 at 180 days). Those who were treated within 90 minutes also appeared to benefit (OR, 1.82), although these results were not significant.

In exploratory analyses, the positive signals in mRS were more apparent at 90 days among both patients with a spot sign (OR, 2.52) and those treated within 90 minutes (OR, 2.66), with the greatest potential benefit in patients who had both a spot sign on CT angiography and treatment within 90 minutes.

Patients in both subgroups also experienced less hematoma expansion with factor VIIa treatment. Compared with placebo, treatment was associated with a 14-mL vs 2.7-mL reduction in combined ICH and IVH growth among individuals with vs without a positive spot sign.

Similarly, those treated within 90 minutes vs after 90 minutes of symptom onset had a 7.5-mL vs 4.3-mL reduction in ICH plus IVH growth.

Broderick said he is hopeful that these results can be confirmed in the FASTEST-2 trial, which is specifically enrolling patients from these two patient groups.

He acknowledged that this represents only a small proportion of patients with ICH (approximately 5%), but he believes that numbers could increase over time.

Broderick drew parallels with the early experience of thrombolysis in ischemic stroke.

“Originally when thrombolysis with alteplase was first approved, we only treated 1% of people with ischemic stroke but this rose dramatically over time as we learned about other populations who can benefit with imaging. We also got better at treating more quickly. So I think if we can get a foothold, use will eventually expand to more patients,” he said.

He emphasized the importance of matching treatment to biology and patient selection. “When biology gives us something like this, we can use technology to identify the right patients to target. Factor VIIa is a very powerful hemostatic drug. It works well, but we need to identify the appropriate patients.”

He added that timing remains critical: “The key appears to be very early treatment. So as is the case for all stroke, it is vitally important that the population recognizes symptoms and gets help fast.”

He said the findings reinforce the importance of early intervention, noting that rapid recognition of stroke symptoms and timely treatment remain critical.

‘An Incredible Accomplishment’

Commenting on the trial for Medscape Medical News, Vice Chair Lauren Sansing, MD, professor of neurology at Yale School of Medicine, New Haven, Connecticut, said the trial was “an incredible accomplishment.”

“The investigators deserve huge kudos for running such a hyperacute trial, randomizing ICH patients in the first 2 hours, and for now persevering with another trial in the promising subgroups.”

She said she is optimistic that factor VIIa could be of benefit for patients in those subgroups.

“We have to be cautious as subgroup analyses have led us astray in the past, but there is a lot of biological plausibility here and data to support that these groups have the highest likelihood to benefit. So I’m thrilled that we’ll have an answer quickly on this from FASTEST-2.”

Sansing noted that the treatment would be relevant to only a small fraction of patients with ICH, given delays in symptom recognition and presentation, but said the results look very promising for those who arrive early enough to be treated.

In an accompanying editorial, Craig Anderson, MD, of the George Institute for Global Health in Sydney, Australia, and colleagues highlighted several challenges encountered in earlier studies of factor VIIa for the treatment of ICH.

They noted that in a previous trial, factor VIIa administered within 4 hours of ICH onset reduced hematoma expansion but did not improve functional outcomes and was associated with an increased risk for serious thromboembolic complications.

They added that if the FASTEST-2 trial does show benefit with ultra-early treatment, that would be an accomplishment, but they pointed out that “generalizability will be minimal worldwide unless code ICH care pathways can identify people with hyperacute ICH in the ambulance and convey them rapidly to hospital, where CT angiography will need to be available, as well as fast-care bundles to effectively control elevated blood pressure and other physiological parameters.”

The FASTEST trial was funded by the US National Institute of Neurological Diseases and Stroke, the Japan Agency for Medical Research and Development, and Novo Nordisk. Broderick, Sansing, Anderson, and colleagues reported having no relevant disclosures.