If you wish to read about meningococcemia try this
4th International Congress
on the Immune Consequences of Trauma,
Shock and Sepsis-Mechanisms
and Therapeutic Approaches
March 4th - 8th, 1997, Munich, Klinikum Grosshadern
Phase I/II Trial of rBPI-21 (a Recombinant 21kD Fragment of Bactericidal/Permeability-Increasing Protein) in Children with Severe Meningococcemia.
E. Kirsch, P. Quint, S. Carroll, P. Scannon, B. Giroir, and the BPI Study Group. UTSW, Dallas, TX; Legacy Emmanuel Children's Hospital, Portland, OR; XOMA Corp., Berkeley, CA and the BPI Study Group Centers.
We conducted an open-label, dose-escalation trial of rBPI-21 plus conventional therapy in children (ages 1-18 years) with severe meningococcemia (GMSPS >= 8), who were administered rBPI-21 infusion within 8 hours of the initial antibiotic. rBPI-21 was administered as an i.v. loading dose (0.5, 1.0, or 2.0 mg/kg) over 30 min. followed by a continuous infusion delivering the same dose (0.5, 1.0, or 2.0 mg/kg) over 24 hours.
26 patients were enrolled between June 1995 and October 1996 in 7 pediatric hospitals in the United States: complete follow-up and data are available for 23 patients (mean age 7 yrs. range 1-18 years; mean wt 35 kg, range 10-154 kg). Diagnosis was microbiologically confirmed in 88% of cases. The mean GMSPS score was 12 (range 8-15). Pre-study plasma samples demonstrated significant elevations in endotoxin (median 371 pg/ml, range 10-970 pg/ml), TNF-alpha (median 40 pg/ml, range 20-471 pg/ml), and IL-6 (median 9,405 pg/ml, range 10-871,000 pg/ml).
The mean time from admission to the study center and initiation of rBPI-21 infusion was 3.2 hours, and the mean time from the first dose of parenteral antibiotics to onset of rBPI-21 infusion was 4.4 hours. rBPI-21 loading infusion resulted in mean peak BPI levels of 673, 23673 and 10,109 ng/ml following 0.5, 1.0, and 2.0 mg/kg load, respectively, and mean steady-state levels of 45, 66, and 165 ng/ml during the continuous infusion. Termination of the infusion was followed by rapid clearance of the protein and decline to endogenous levels of BPI by two hours after the rBPI-21 infusion. No acute hemodynamic effects were noted during the loading infusions, and all clinical and laboratory changes were consistent with the underlying disease.
Of 26 patients receiving rBPI-21, 25 have survived (mortality 4%). Historical data is comparable patients form trial centers (1993-95), as well as published prognostic criteria from other studies (GMSPS score, coagulopathy, or levels of endotoxin or cytokines), predict a mortality in the range of 20% - 50%. These data suggest a marked biologic effect of rBPI-21 in children with severe meningococcemia. A Phase III Trail has been initiated.
The University of Texas Southwestern Medical Center, Department of Pediatrics, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9063, U.S.A.
*******************I believe they will be publishing the full data in a journal within months
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