PMID- 16757825
OWN - NLM
STAT- MEDLINE
DCOM- 20060912
LR  - 20181113
IS  - 1541-6933 (Print)
IS  - 1541-6933 (Linking)
VI  - 4
IP  - 3
DP  - 2006
TI  - Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA 
      trial.
PG  - 206-14
AB  - 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.
FAU - Mayer, Stephan A
AU  - Mayer SA
AD  - Department of Neurology, Columbia University College of Physicians & Surgeons, 
      New York, NY, USA. sam14@columbia.edu
FAU - Brun, Nikolai C
AU  - Brun NC
FAU - Broderick, Joseph
AU  - Broderick J
FAU - Davis, Stephen M
AU  - Davis SM
FAU - Diringer, Michael N
AU  - Diringer MN
FAU - Skolnick, Brett E
AU  - Skolnick BE
FAU - Steiner, Thorsten
AU  - Steiner T
CN  - United States NovoSeven ICH Trial Investigators
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurocrit Care
JT  - Neurocritical care
JID - 101156086
RN  - 0 (Hemostatics)
RN  - 0 (Recombinant Proteins)
RN  - 9001-25-6 (Factor VII)
RN  - AC71R787OV (recombinant FVIIa)
RN  - EC 3.4.21.21 (Factor VIIa)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cerebral Hemorrhage/complications/diagnostic imaging/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Factor VII/*administration & dosage/adverse effects
MH  - Factor VIIa
MH  - Feasibility Studies
MH  - Female
MH  - Hematoma/diagnostic imaging/etiology/*prevention & control
MH  - Hemostatics/*administration & dosage/adverse effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Radiography
MH  - Recombinant Proteins/administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - United States
EDAT- 2006/06/08 09:00
MHDA- 2006/09/13 09:00
CRDT- 2006/06/08 09:00
PHST- 1999/11/30 00:00 [received]
PHST- 1999/11/30 00:00 [revised]
PHST- 1999/11/30 00:00 [accepted]
PHST- 2006/06/08 09:00 [pubmed]
PHST- 2006/09/13 09:00 [medline]
PHST- 2006/06/08 09:00 [entrez]
AID - NCC:4:3:206 [pii]
AID - 10.1385/NCC:4:3:206 [doi]
PST - ppublish
SO  - Neurocrit Care. 2006;4(3):206-14. doi: 10.1385/NCC:4:3:206.