FASTEST
(2026)Objective
To evaluate whether recombinant factor VIIa (80 µg/kg IV) administered within 2 hours of symptom onset improves functional outcome at 180 days in adults with acute spontaneous intracerebral haemorrhage.
Study Summary
• rFVIIa significantly slowed haematoma growth: ICH volume change was -3.7 mL less than placebo (95% CI -5.4 to -1.9, p=0.0011) and ICH+IVH growth was -5.2 mL less (p=0.0011).
• rFVIIa increased life-threatening thromboembolic complications within 4 days: 15 (<5%) vs 4 (1%); relative risk 3.41 (95% CI 1.14-10.15, p=0.020).
• Subgroup signals (non-significant): patients with a CT angiography spot sign (OR 1.86) or treated within 90 min (OR 1.82) showed numerical trends favoring rFVIIa; combination of both showed greatest exploratory benefit.
Intervention
Recombinant factor VIIa 80 µg/kg IV over 2 min (max 10 mg) vs identical placebo IV within 2 hours of ICH onset
Inclusion Criteria
Adults 18-80 years with spontaneous ICH 2-60 mL, IVH in less than two-thirds of one lateral ventricle or less than one-third of both, GCS >=8, no recent anticoagulants, treated within 2 hours of symptom onset or last known well
Study Design
Arms: Recombinant factor VIIa 80 µg/kg IV (n=328) vs Placebo (n=298)
Patients per Arm: 328 rFVIIa, 298 placebo (626 total)
Outcome
• rFVIIa did significantly reduce haematoma growth (ICH volume: -3.7 mL vs placebo, p=0.0011) but this did not translate to functional benefit.
• Safety concern: 3-fold increased risk of life-threatening thromboembolic events within 4 days (5% vs 1%, RR 3.41, p=0.020).
Bottom Line
Recombinant factor VIIa 80 µg/kg given within 2 hours of ICH onset significantly slowed haematoma growth but did not improve functional outcomes at 180 days and was associated with a 3-fold increased risk of life-threatening thromboembolic events. The trial was stopped for futility. Subgroup signals in patients with a CT spot sign or treated within 90 minutes are hypothesis-generating and being investigated in FASTEST part 2.
Major Points
- No improvement in functional outcome: mRS distribution at 180 days was identical between groups (OR 1.09, 95% CI 0.79-1.51, p=0.61); trial stopped for futility at second interim analysis (conditional power <1%).
- rFVIIa significantly slowed haematoma growth: ICH volume change from baseline to 24h was -3.7 mL less with rFVIIa (p=0.0011) and ICH+IVH growth was -5.2 mL less (p=0.0011).
- Slowing bleeding did not translate to improved outcomes, suggesting that a mean reduction of ~3-4 mL may be insufficient; modelling suggests 6-12 mL may be needed to improve functional outcomes.
- Life-threatening thromboembolic complications within 4 days were significantly higher with rFVIIa: 15 (<5%) vs 4 (1%), RR 3.41 (95% CI 1.14-10.15, p=0.020).
- Subgroup signals (non-significant but prespecified): spot sign OR 1.86 (0.94-3.68) and treatment within 90 min OR 1.82 (0.98-3.40) -- patients with both features showed the greatest exploratory benefit.
- Adaptive enrichment to age <=70 years was added during the trial but also showed no benefit (conditional power <1%).
- FASTEST part 2 (NCT07227246) is ongoing, recruiting additional sites specifically targeting patients with a spot sign or treated within 90 min.
- CT angiography should be integrated into standard ICH assessment workflows to rapidly identify patients with spot signs and ongoing bleeding risk.
Study Design
- Study Type
- Multicentre, double-blind, randomised, placebo-controlled, adaptive, phase 3 trial
- Randomization
- Yes
- Blinding
- Double-blind (all investigators and participants masked)
- Sample Size
- 626
- Follow-up
- 180 days
- Centers
- 93
- Countries
- USA, Japan, Canada, Spain, Germany, UK
Primary Outcome
Definition: Ordinal modified Rankin Scale (mRS 0-2, 3, and 4-6) at 180 days, measured by Rankin Focused Assessment Tool; analysed by ordinal logistic regression
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 134/298 (45%) mRS 0-2; 76/298 (26%) mRS 3; 88/298 (30%) mRS 4-6 | 151/328 (46%) mRS 0-2; 80/328 (24%) mRS 3; 97/328 (30%) mRS 4-6 | 1.09 (0.79 to 1.51) | 0.61 |
Limitations & Criticisms
- Trial stopped early for futility -- underpowered for subgroup analyses, which remain exploratory
- Mean haematoma growth reduction (~3.5 mL) appears insufficient; modelling suggests 6-12 mL may be needed to improve functional outcomes
- Thromboembolic risk is a real and significant concern -- limits widespread use even if efficacy were confirmed
- Asian patients comprised ~55% of the sample (due to Japan enrollment); findings may not be fully generalisable to other populations given different ICH etiologies (hypertensive-dominant in Japan vs more diverse in USA)
- Adaptive enrichment to younger patients (<=70 years) was added mid-trial but also showed no benefit, reducing confidence in age-based patient selection
- Only 45% of participants received treatment within 90 min or had a spot sign -- the 'ideal' subgroup was a minority, limiting the ability to test these hypotheses definitively
- Emergency consent procedures and mobile stroke units add operational complexity not universally available
Citation
Lancet. 2026;407:773-783