Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus.

Abstract

AIM:

Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the cerebrospinal fluid, and thus preventing permanent hydrocephalus.

METHODS:

Twenty two preterm infants, aged 7 to 26 days, with progressive posthaemorrhagic ventricular dilatation (ventricular width > 4 mm over 97th centile) received one to five intraventricular bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to seven days.

RESULTS:

The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 micrograms/ml. The half life of tPA in cerebrospinal fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55%) without shunt surgery. One infant had secondary intraventricular haemorrhage.

CONCLUSION:

Intraventricular tPA resulted in survival without a shunt for most of the infants, but with some risk. Failure may have been due to plasminogen deficiency, an inhibitor, or late intervention.

• Authors: A Whitelaw, E Saliba, V Fellman, M C Mowinckel, D Acolet, N Marlow
• Journal: Archives of disease in childhood. Fetal and neonatal edition (Arch Dis Child Fetal Neonatal Ed) Vol. 75 Issue 1 Pg. F20-6 (Jul 1996) ISSN: 1359-2998 [Print] England
• PMID: 8795351 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Plasminogen Activators
• Tissue Plasminogen Activator

Topics

• Cerebral Hemorrhage (cerebrospinal fluid, drug therapy)
• Half-Life
• Humans
• Hydrocephalus (cerebrospinal fluid, drug therapy)
• Infant, Newborn
• Infant, Premature
• Infant, Premature, Diseases (cerebrospinal fluid, drug therapy)
• Injections, Intraventricular
• Plasminogen Activators (administration & dosage, cerebrospinal fluid, therapeutic use)
• Recombinant Proteins (administration & dosage, therapeutic use)
• Tissue Plasminogen Activator (administration & dosage, cerebrospinal fluid, therapeutic use)