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

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, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/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 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg 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.

• Authors: Stephan A Mayer, Nikolai C Brun, Joseph Broderick, Stephen M Davis, Michael N Diringer, Brett E Skolnick, Thorsten Steiner, United States NovoSeven ICH Trial Investigators
• Journal: Neurocritical care (Neurocrit Care) Vol. 4 Issue 3 Pg. 206-14 ( 2006) ISSN: 1541-6933 [Print] United States
• PMID: 16757825 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hemostatics
• Recombinant Proteins
• Factor VII
• recombinant FVIIa
• Factor VIIa

Topics

• Adult
• Aged
• Aged, 80 and over
• Cerebral Hemorrhage (complications, diagnostic imaging, drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Factor VII (administration & dosage, adverse effects)
• Factor VIIa
• Feasibility Studies
• Female
• Hematoma (diagnostic imaging, etiology, prevention & control)
• Hemostatics (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Radiography
• Recombinant Proteins (administration & dosage, adverse effects)
• Treatment Outcome
• United States