Treatment of acute stroke with recombinant tissue plasminogen activator and abciximab.
OBJECTIVE
Preclinical data suggest that treatment of acute ischemic stroke (AIS) with the combination of recombinant tissue plasminogen activator (rt-PA) and abciximab may increase efficacy and decrease the rate of symptomatic intracranial hemorrhage (sICH). The authors report pilot data of five AIS patients with half-dose rt-PA and abciximab as part of an ongoing phase I safety trial with sICH as the primary outcome.


METHODS
Five patients with AIS were treated with the combination of half-dose rt-PA (0.45 mg/kg) and abciximab (0.25 mg/kg bolus followed by a 0.125 microg/kg/min infusion over 12 hours). Head computed tomographic scan was obtained after 24 hours of treatment onset.


RESULTS
Four patients received the combination of half-dose abciximab and rt-PA without major complications. One patient experienced a parenchymal hematoma type-1 ICH without significant decline of his neurological status. The average National Institutes of Health Stroke Scale change at discharge in comparison with pretreatment was -5.4 +/- 7.0, and the median change was 6 points with a range of 4 points (worsening) to -13 points (improvement) (p=0.07) based on a one-sided t-test.


CONCLUSIONS
Administration of rt-PA and abciximab to AIS patients was completed without difficulty. No sICH were observed; however, 20% (1 out of 5) experienced an asymptomatic ICH. Based on our observation of five patients, there was a trend of treatment efficacy; however, these results need to be confirmed in a larger-scale placebo-controlled clinical trial.
Morris
Daniel C
DC
Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USA. morris@neuro.hfh.edu
Silver
Brian
B
Mitsias
Panos
P
Lewandowski
Christopher
C
Patel
Suresh
S
Daley
Sheila
S
Zhang
Zheng G
ZG
Lu
Mei
M
D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D000077284:Abciximab