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Previous Volume 358:2127-2137 May 15, 2008 Number 20 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Tuhrim, S. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.

Methods We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 µg of rFVIIa per kilogram of body weight (276 patients), or 80 µg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.

Results Treatment with 80 µg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 µg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 µg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], –0.3 to 5.5; P=0.08) in the group receiving 20 µg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 µg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 µg of rFVIIa per kilogram, and 29% in the group receiving 80 µg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 µg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).

Conclusions Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov] .)

Source Information

From the Departments of Neurology and Neurosurgery, Columbia University College of Physicians and Surgeons, New York (S.A.M.); Novo Nordisk, Bagsvaerd, Denmark (N.C.B., K.B.); the University of Cincinnati Medical Center, Cincinnati (J.B.); the Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia (S.D.); Washington University School of Medicine, St. Louis (M.N.D.); Novo Nordisk, Princeton, NJ (B.E.S.); and the University of Heidelberg, Heidelberg, Germany (T.S.).

Address reprint requests to Dr. Mayer at the Neurological Institute, 710 W. 168th St., Box 39, New York, NY 10032, or at sam14{at}columbia.edu.

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