Urgent therapy for stroke part I. Pilot study of tissue plasminogen activator administered within 90 minutes

Thomas G. Brott, E. Clarke Haley, David E. Levy, William Barsan, Joseph Broderick, George L. Sheppard, Judith Spilker, Gail L. Kongable, Sandra Massey, Robert Reed, John R. Marler

Research output: Contribution to journalArticlepeer-review

433 Scopus citations


Background and Purpose: Ttarombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator. Methods: Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months. Results: Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p=0.045). Intracranial hematoma did not occur in any of the 58 patients treated with ≤ 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type. Conclusions: Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.

Original languageEnglish (US)
Pages (from-to)632-640
Number of pages9
Issue number5
StatePublished - May 1992


  • Cerebral ischemia
  • Plasminogen activator
  • Thrombolytic therapy
  • Tissue-type

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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