PMID- 15569871
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20161124
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 36
IP  - 1
DP  - 2005 Jan
TI  - Safety and feasibility of recombinant factor VIIa for acute intracerebral 
      hemorrhage.
PG  - 74-9
AB  - BACKGROUND AND PURPOSE: Hematoma growth occurs in 38% of intracerebral hemorrhage 
      (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. 
      Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of 
      vascular injury and may minimize hematoma growth after ICH. METHODS: In this 
      randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects 
      with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or 
      rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary 
      endpoint was the frequency of adverse events (AEs). Safety assessments included 
      serial electrocardiography (ECG), troponin I and coagulation testing, lower 
      extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. 
      RESULTS: Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, 
      mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 
      26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume 
      was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes 
      (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 
      11%). Six AEs were considered possibly treatment-related, including rash, 
      vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis 
      (placebo and 20-microg/kg groups). No myocardial ischemia, consumption 
      coagulopathy, or dose-related increase in edema:ICH volume occurred. CONCLUSIONS: 
      This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and 
      raised no major safety concerns. Larger studies are justified to determine 
      whether rFVIIa can safely and effectively limit ICH growth.
FAU - Mayer, Stephan A
AU  - Mayer SA
AD  - Department of Neurology, Columbia University College of Physicians and Surgeons, 
      New York, NY, USA. sam14@columbia.edu
FAU - Brun, Nikolai C
AU  - Brun NC
FAU - Broderick, Joseph
AU  - Broderick J
FAU - Davis, Stephen
AU  - Davis S
FAU - Diringer, Michael N
AU  - Diringer MN
FAU - Skolnick, Brett E
AU  - Skolnick BE
FAU - Steiner, Thorsten
AU  - Steiner T
CN  - Europe/AustralAsia NovoSeven ICH Trial Investigators
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20041129
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Hemostatics)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.21.21 (Factor VIIa)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Aged
MH  - Blood Coagulation Tests
MH  - Brain Edema/diagnostic imaging
MH  - Cerebral Hemorrhage/diagnosis/diagnostic imaging/*drug therapy
MH  - Double-Blind Method
MH  - Factor VIIa/*adverse effects/genetics/therapeutic use
MH  - Female
MH  - Hematoma/prevention & control
MH  - Hemostatics/administration & dosage/*adverse effects/therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Recombinant Proteins/adverse effects/therapeutic use
MH  - Tomography, X-Ray Computed
EDAT- 2004/12/01 09:00
MHDA- 2005/09/02 09:00
CRDT- 2004/12/01 09:00
PHST- 2004/12/01 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2004/12/01 09:00 [entrez]
AID - 01.STR.0000149628.80251.b8 [pii]
AID - 10.1161/01.STR.0000149628.80251.b8 [doi]
PST - ppublish
SO  - Stroke. 2005 Jan;36(1):74-9. doi: 10.1161/01.STR.0000149628.80251.b8. Epub 2004 
      Nov 29.