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


CONCLUSIONS
Preliminary analyses show that use of low-dose rt-PA can be safely administered to stable IVH clots and may increase lysis rates.
Morgan
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Johns Hopkins University, 1550 Orleans Street, CRB II 3M50 South, Baltimore, MD 21231, USA. tmorga10@jhmi.edu
Awad
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Keyl
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Lane
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Hanley
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D000293:Adolescent; D000328:Adult; D000368:Aged; D002533:Cerebral Angiography; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000601:surgery; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator