Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial

Stephan A. Mayer, Nikolai C. Brun, Joseph Broderick, Stephen M. Davis, Michael N. Diringer, Brett E. Skolnick, Thorsten Steiner

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Background and Purpose: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven®) for preventing early hematoma growth in acute ICH. Methods: In this multicenter, randomized, double-blind, placebo-controlled, doseescalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 μg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). Results: Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 ± 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 ± 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 μg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 μg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 μg g/kg [ n = 1], 40 μg g/kg [ n = 1], and 80 μg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. Conclusions: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.

Original languageEnglish
Pages (from-to)206-214
Number of pages9
JournalNeurocritical Care
Volume4
Issue number3
DOIs
StatePublished - Jun 2006

Keywords

  • Coagulation
  • Emergency stroke treatment
  • Hemostasis
  • Intracerebral hemorrhage
  • Recombinant activated factor VII

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