Intra-arterial reteplase and intravenous abciximab in patients with acute ischemic stroke: an open-label, dose-ranging, phase I study

Neurosurgery. 2006 Oct;59(4):789-96; discussion 796-7. doi: 10.1227/01.NEU.0000232862.06246.3D.

Abstract

Objective: New approaches are focusing on using a combination of medication that lyse fibrin and prevent aggregation of platelets to achieve higher rates of recanalization and improved clinical outcomes.

Methods: A prospective, nonrandomized, open-label trial evaluated the safety of an escalating dose of reteplase in conjunction with intravenous abciximab (platelet glycoprotein IIb/IIIa inhibitor) in patients with acute ischemic stroke (3-6 h after symptom onset). The primary endpoint was symptomatic intracerebral hemorrhage at 24 to 72 hours, and secondary endpoints were partial or complete recanalization (> or = one grade improvement), early neurological improvement (decrease in National Institutes of Health Stroke Scale > or = 4 at 24 h), and favorable outcome at 1 month (defined by modified Rankin scale < or = 2).

Results: A total of 20 patients (mean age, 65 yr; 13 men) were recruited. Five patients were recruited in each of the escalating tiers of intra-arterial reteplase (0.5, 1, 1.5, and 2 units). Intravenous abciximab (0.25 mg/kg bolus followed by 0.125 mug/kg/min) was successfully administered in 18 out of 20 patients. The safety stopping rule was not activated in any of the tiers. One symptomatic intracerebral hemorrhage was observed in one of the 20 patients (in the 1-unit tier). Partial or complete recanalization was observed in 13 of the 20 patients. Thirteen patients demonstrated early neurological improvement, and favorable outcome at 1 month was observed in six patients.

Conclusion: In this study, a combination of intra-arterial reteplase and intravenous abciximab was safely administered to patients with ischemic stroke presenting between 3 and 6 hours after symptom onset.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abciximab
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Arterial Occlusive Diseases / complications
  • Arterial Occlusive Diseases / diagnostic imaging
  • Brain Ischemia / complications*
  • Carotid Arteries
  • Cerebral Angiography
  • Cerebral Hemorrhage / chemically induced
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage*
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use
  • Injections, Intra-Arterial
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Stroke / drug therapy*
  • Stroke / etiology*
  • Stroke / mortality
  • Tissue Plasminogen Activator / administration & dosage*
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Fibrinolytic Agents
  • Immunoglobulin Fab Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • reteplase
  • Tissue Plasminogen Activator
  • Abciximab