Correspondence to Gregory J. del Zoppo, MD, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N Torrey Pines Rd, SBR-17, La Jolla, CA 92037. E-mail grgdlzop{at}riscsm.scripps.edu
Background and Purpose—To test the
safety and recanalization efficacy of
intra-arterial local delivery of plasminogen
activators in acute ischemic stroke, a randomized
trial of recombinant pro-urokinase (rpro-UK) versus placebo was
undertaken in patients with angiographically documented proximal middle
cerebral artery occlusion.
Methods—After exclusion of intracranial hemorrhage by CT
scan, patients with abrupt onset of symptoms of focal ischemia
likely to receive treatment within 6 hours who satisfied all clinical
eligibility criteria underwent carotid angiography. Patients displaying
Thrombolysis in Acute Myocardial Infarction grade 0 or 1
occlusion of the M1 or M2 middle cerebral artery were randomized 2:1 to
receive rpro-UK (6 mg) or placebo over 120 minutes into the proximal
thrombus face. All patients received intravenous heparin.
Recanalization efficacy was assessed at the end of
the 2-hour infusion, and intracerebral
hemorrhage causing neurological deterioration was assessed at
24 hours.
Results—Of 105 patients who underwent angiography, 59 were
excluded from randomization. Among the 46 patients randomized, 40 were
treated with rpro-UK (n=26) or placebo (n=14) a median of 5.5 hours
from symptom onset. Recanalization was
significantly associated with rpro-UK (2P=.017).
Hemorrhagic transformation causing neurological deterioration within 24
hours of treatment occurred in 15.4% of the rpro-UK–treated patients
and 7.1% of the placebo-treated patients (2P=.64). Both
recanalization and hemorrhage frequencies
were influenced by heparin dose.
Conclusions—Intra-arterial local rpro-UK infusion was
associated with superior recanalization in acute
thrombotic/thromboembolic stroke compared with placebo. In this
regimen, heparin dose influenced hemorrhage frequency and
recanalization. Although symptomatic
hemorrhage remains a concern, this study suggests that
recanalization is enhanced with rpro-UK and
heparin.
© 1998 American Heart Association, Inc.
Original Contributions
PROACT: A Phase II Randomized Trial of Recombinant Pro-Urokinase by Direct Arterial Delivery in Acute Middle Cerebral Artery Stroke
Key Words: stroke, acute • angiography • hemorrhage • pro-urokinase • recanalization
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