Subgroup Signals Emerge for rFVIIa in Acute Intracerebral Hemorrhage in Phase 3 FASTEST Trial

Late-breaking results from the phase 3 FASTEST trial (NCT03496883) showed that recombinant factor VIIa (rFVIIa) given within 2 hours of intracerebral hemorrhage onset slowed hematoma growth but did not improve overall functional outcomes and carried a small increased risk of life-threatening thromboembolic events. Treatment effects were most evident in higher-risk subgroups, including patients with a CT angiography spot sign or those treated within 90 minutes, where greater bleeding control was linked to signals of longer-term efficacy.¹

Presented at the 2026 International Stroke Conference (ISC), held February 4-6 in New Orleans, Louisiana, FASTEST was a double-blind trial that randomized 626 patients with ICH across 100 hospitals in 5 countries, while incorporating 15 different mobile stroke units into the study protocol. In Part 1 of the study, patients were randomly assigned 1:1 to intravenous rFVIIa or placebo at a dose of 80 ug/kg (maximum 10,000 ug or 10 mg), using 180-day modified Rankin Scale (mRS) scores as the primary outcome.

Led by Joseph Broderick, MD, director of the UC Gardner Neuroscience Institute at the University of Cincinnati Academic Health Center and director of the National NIH StrokeNet, 46.0% (n = 151) of rFVIIa-treated patients achieved mRS scores of 0-2 compared with 45% (n = 134) of those on placebo in the intent-to-treat (ITT) population. Results continued to stay stagnant when looking at the per protocol population, which comprised 594 participants (placebo mRS 0-2: 45.1%; rFVIIa: 47.4%).

Using regression models, investigators recorded a 5.53 (SD, 13.68)-point change in ICH volume, a secondary outcome, from baseline to 24 hours in placebo-treated patients vs just 1.85 (SD, 6.964) for the rFVIIa group. When looking at change in ICH and intraventricular hemorrhage (IVH) volume, investigators recorded changes of 7.41 (SD, 19.569) and 2.18 (SD, 8.427) for the placebo and rFVIIa groups, respectively.

When looking at safety outcomes, life-threatening thromboembolic complications within 4 days were noticeably more frequent in the active treatment group (4.6%; n = 15) than placebo (1.3%; n = 4; relative risk, 3.41; 95% CI, 1.14-10.15; P = .02). In the study, there were higher rates of life-threatening thromboembolic complications within 90 days (6.4% vs 3.7%), myocardial injury without acute coronary syndrome (14.9% vs 10.1%), and acute cerebral infarction (5.5% vs 3.7%) in the rFVIIa group. Notably, mortality rates were about the same between the two groups (rVIIa: 6.1%; placebo: 7.4%).

READ MORE: CREST-2 Substudy Shows No Cognitive Benefit of Carotid Revascularization in Asymptomatic Carotid Stenosis

Despite the lack of functional improvement over 90 days, the study did find certain subgroups perform better than others. On the primary outcome of mRS change, those with within 90 minutes of last known normal showed greater outcomes (odds ratio [OR], 1.82; 95% CI, 0.98-3.4), as well as those with at least 1 spot sign (OR, 1.86; 95% CI, 0.94-3.68).

When looking at patients who had spot sign on CTA, there was a mean difference of –14.14 (95% CI, –20.68 to –7.60) in growth of ICH+IVH for rFVIIa-treated patients relative to placebo. For comparison, there was only a –2.67 (95% CI, –5.11 to –0.23) mean difference observed for those with no spot sign. Similarly, when comparing patients seen before and after the 90-minute window, there was a mean treatment-group ICH+IVH difference of –7.56 (95% CI, –11.86 to –3.27) for those under the 90-minute window vs –4.30 (95% CI, –7.21 to –1.40) for those outside of this window.

Continuing on with subgroups, there was a 38% absolute difference of moderate and major hemorrhage enlargement (HE) among spot sign participants who were treated with rFVIIa compared with placebo. In addition, major HE (>12.5 mL) was found in 14.0% of rVIIa-treated patients vs 32.4% of those on placebo. For those treated within 90 minutes, there was a 20% absolute difference in moderate and major growth of HE for those who received rFVIIa vs placebo.

FASTEST Part 2, a trial of rFVIIa in patients with ICH treated within 90 minutes or with a positive spot sign within 120 minutes, is currently ongoing. Part 2 of the FASTEST trial builds on signals observed in the initial phase, focusing enrollment on patients with the highest likelihood of hematoma expansion and potential treatment response. Eligible participants include adults aged 18 to 80 years with spontaneous ICH volumes between 2 and 60 cc, limited intraventricular extension, and a Glasgow Coma Scale score of at least 8. Enrollment prioritizes those with a baseline CT angiography spot sign treated within 120 minutes of onset, as well as patients treated within 90 minutes regardless of spot sign status, reflecting subgroups in Part 1 where biologic and clinical signals were strongest.²

To achieve ultra-early treatment, the trial incorporates emergency research consent pathways, including exception from informed consent in the United States, and leverages mobile stroke units alongside high-volume global centers capable of rapid ICH care. Approximately 100 hospital sites and at least 15 mobile stroke units are participating, with a goal of treating half of enrolled patients within 90 minutes. Investigators plan to recruit up to 350 participants over roughly three and a half years.

REFERENCES
1. Broderick, J, Grotta J, Naidech A, et al. rFVIIa for Acute hemorrhagic Stroke Administered at Earliest Time. Presented at: 2026 ISC Conference; February 4-6; New Orleans, LA.
2. Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial - Part 2 (FASTEST Part 2). Clincialtrials.gov. Updated January 27, 2026. Accessed February 4, 2026. https://clinicaltrials.gov/study/NCT07227246