The New England Journal of Medicine ( NEJM ) reports positive results from the clinical trial of recombinant activated factor VII ( NovoSeven/rFVIIa ) in intracerebral haemorrhage (ICH ).

The trial was designed to determine if a reduction in haematoma growth might be achieved by administration of the haemostatic agent rFVIIa and to evaluate whether limiting haemorrhage growth had significant impact on improving patient clinical outcomes.

The NEJM article reports encouraging results from the trial demonstrating that early administration of rFVIIa was associated with reduced haematoma growth and improved clinical outcome.

The trial included 399 patients, all diagnosed by a CT scan within three hours of ICH onset. Patients were randomly assigned to receive placebo (N=96), 40 (N=108), 80 (N=92) or 160 (N=103) µg/kg doses of rFVIIa within one hour of the baseline scan. The primary outcome measure was the percentage change in ICH volume at 24 hours after treatment. Clinical and neurological outcomes were assessed at 90 days after treatment.

Key findings included:

· Primary end point: statistically significant reduction in haematoma growth

Compared to 29% growth in placebo-treated patients, ICH volume growth in the 40, 80 and 160 µg/kg treatment groups was 16%, 14% and 11% respectively (corresponding to a relative reduction of 45%, 52% and 62%).

· Secondary end points: statistically significant improvement in neurological and clinical outcome

69% of placebo-treated patients died or were severely disabled at 90 days after dosing (modified Rankin Scale (mRS) score 4–6[7]), compared to 55%, 49% and 54% of the rFVIIa-treated patients. Receiving rFVIIa more than doubled a patient’s chances of improving one level on the mRS.

This led to a 16% absolute reduction in the risk of death or severe disability at three months according to the mRS.

Mortality was 38% lower ( p=0.02) in the combined rFVIIa-treated groups compared to placebo.

· Safety end points:

The overall frequency of fatal or disabling thromboembolic serious adverse events did not differ between the rFVIIa ( 2.0% ) and the placebo ( 2.1% ) groups. However, arterial thromboembolic serious adverse events occurred statistically significantly more frequently with rFVIIa treatment ( 5% ) than with placebo ( 0% ), manifesting in the form of myocardial ischaemic events and cerebral infarction. The majority of patients recovered from these complications.

Overall, the trial results indicate that early administration of rFVIIa to patients with ICH may limit haematoma growth, reduce mortality and improve neurological and clinical outcomes without significantly raising the risk of fatal or disabling thromboembolic complications.

Source: The New England Journal of Medicine, 2005

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