Argatroban tPA stroke study: study design and results in the first treated cohort

Arch Neurol. 2006 Aug;63(8):1057-62. doi: 10.1001/archneur.63.8.1057.

Abstract

Background: The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute stroke is linked to clot lysis and artery recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. There are no human data on this combination.

Design: We report the first phase of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose-escalation, safety and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours. After standard-dose intravenous rtPA administration, a 100-mug/kg bolus of argatroban followed by infusion of 1 mug/kg per minute for 48 hours was adjusted to a target partial thromboplastin time of 1.75 times that of the control group.

Results: Fifteen patients (including 10 men) were enrolled, with a mean +/- SD age of 61 +/- 13 years. All patients had middle cerebral artery occlusions. Baseline median National Institute of Health Stroke Scale score was 14 (range, 4-25). The mean +/- SD time from symptom onset to argatroban bolus administration was 172 +/- 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 1 patient and there was 1 death. Recanalization was complete in 6 patients and partial in another 4, and reocclusion occurred in 3 within 2 hours of rtPA bolus administration.

Conclusion: The safety of low-dose argatroban combined with intravenous rtPA may be within acceptable limits, and its efficacy for producing fast and complete recanalization is promising, but a larger cohort of patients is required to confirm these preliminary observations.

Trial registration: ClinicalTrials.gov NCT00268762.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / pathology
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pipecolic Acids / administration & dosage*
  • Pipecolic Acids / adverse effects
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Research Design
  • Stroke / drug therapy*
  • Stroke / pathology
  • Sulfonamides
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Pipecolic Acids
  • Recombinant Proteins
  • Sulfonamides
  • Arginine
  • Tissue Plasminogen Activator
  • argatroban

Associated data

  • ClinicalTrials.gov/NCT00268762