Preliminary report of the clot lysis evaluating accelerated resolution of intraventricular hemorrhage (CLEAR-IVH) clinical trial

Acta Neurochir Suppl. 2008:105:217-20. doi: 10.1007/978-3-211-09469-3_41.

Abstract

Introduction: Brain hemorrhage is the most frequent fatal form of stroke and has the highest level of morbidity of any stroke subtype. For patients with both intracerebral hemorrhage and intraventricular hemorrhage (IVH), expected mortality is 50-80%. No validated, efficacious treatment exists for humans, but animal models demonstrate substantial physiologic and functional benefits associated with rapid, near-complete removal of blood from either the ventricle or intracerebral location (i.e., approximately 80% removal over 48 h). The purpose of the CLEAR-IVH trial (Parts A and B) is to evaluate safety and efficacy of using multiple injections of low-dose rt-PA to accelerate lysis and evacuation of IVH.

Methods: Patients enrolled in the trial receive an injection of 1.0 mg rtPA through an external ventricular drain every 8 h up to 12 doses, or until clot reduction or clinical endpoint is met. CT scans are taken daily to monitor clot resolution and check for unexpected bleeding events. In a previous dose-finding study where the safety profile (symptomatic rebleeding) was 0%, 1 mg rt-PA every 8 h was determined the appropriate dose.

Results: Comprehensive analyses of 36 patients in the recently completed CLEAR-IVH Part B are currently being conducted. Adverse events are within safety limits, including 30-day mortality, 8%; symptomatic re-bleeding, 8%; and bacterial ventriculitis, 0%.

Conclusion: Preliminary analyses show that use of low-dose rt-PA can be safely administered to stable IVH clots and may increase lysis rates.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cerebral Angiography
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology*
  • Cerebral Hemorrhage / surgery
  • Cerebral Ventricles / drug effects*
  • Cerebral Ventricles / surgery
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Tissue Plasminogen Activator / therapeutic use*
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator