PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. PROACT Investigators. Prolyse in Acute Cerebral Thromboembolism.

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.
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.
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.
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.
AuthorsG J del Zoppo, R T Higashida, A J Furlan, M S Pessin, H A Rowley, M Gent
JournalStroke; a journal of cerebral circulation (Stroke) Vol. 29 Issue 1 Pg. 4-11 (Jan 1998) ISSN: 0039-2499 [Print] UNITED STATES
PMID9445320 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticoagulants
  • Enzyme Precursors
  • Fibrinolytic Agents
  • Placebos
  • Recombinant Proteins
  • Heparin
  • saruplase
  • Plasminogen Activators
  • Urokinase-Type Plasminogen Activator
  • Acute Disease
  • Aged
  • Anticoagulants (administration & dosage, adverse effects, therapeutic use)
  • Brain Ischemia (drug therapy, radiography)
  • Cerebral Angiography
  • Cerebral Arterial Diseases (drug therapy, radiography)
  • Cerebral Hemorrhage (diagnosis, radiography)
  • Cerebrovascular Disorders (drug therapy, radiography)
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enzyme Precursors (administration & dosage, adverse effects, therapeutic use)
  • Female
  • Fibrinolytic Agents (administration & dosage, adverse effects, therapeutic use)
  • Heparin (administration & dosage, adverse effects, therapeutic use)
  • Humans
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Intracranial Embolism and Thrombosis (drug therapy, radiography)
  • Ischemic Attack, Transient (drug therapy, radiography)
  • Male
  • Neurologic Examination
  • Placebos
  • Plasminogen Activators (administration & dosage, adverse effects, therapeutic use)
  • Recombinant Proteins (administration & dosage, adverse effects, therapeutic use)
  • Safety
  • Time Factors
  • Tomography, X-Ray Computed
  • Urokinase-Type Plasminogen Activator (administration & dosage, adverse effects, therapeutic use)

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