Notes from Dr. Falk's presentation in England. I too, am disappointed and think I will stop asking Xoma first and post instead:
THE BPI TRIALS
Saul Faust MRCP
MRC Clinical Training Fellow (Previously BPI Fellow),
Department of Paediatrics, Imperial School of Medicine at St. Mary's.
What is rBPI?
rBPI21 is a recombinant amino terminal fragment of a basic 55kD protein found in the azurophilic granules of human neutrophils. rBPI21 is bactericidal against several strains of E.coli and has been shown to increase survival and reduce morbidity in rodent and rabbit models of gram negative infections.
The Phase 2 trial
Reported in The Lancet in November 1997, 26 children enrolled in an open label clinical trial we treated with encouraging results using historical controls.
The Phase 3 trial in children
The phase 3 trial is an international multicentre trial taking place at centres in the UK and USA. An independent data review board monitor the study at set intervals to ensure the trial enrols sufficient patients to reach statistical significance. Review of the first 100 patients did not highlight any safety concerns, and currently the final number of patients estimated to be required is 300.
Entry to the trial
All children aged 3 months-18 years are eligible for entry to the trial if they suffer from no existing medical conditions and have a modified Glasgow Meningococcal Prognostic Score (GMSPS) of 8 or above. Entry is stratified into a high (12-15) and low (8-11) GMSPS score. Parenteral antibiotics must have been administered less than 8 hours from the start of the rBPI21 infusion.
Logistical issues
Most patients are enrolled on retrieval at the referring hospital. For ethical and legal purposes, clinical responsibility passes to the retrieval team at arrival at the referring hospital. Informed consent is a prerequisite of entry to the trial.
Current numbers admitted to trial (23rd April 1998)
UK 143 (73%)
of which St. Mary's: 76 (39%)
Guy's: 15 (7.5%)
Liverpool: 15 (7.5%)
Other Centres: 37 (19%)
USA Centres: 52 (27%)
TOTAL 195 (100%)
Centres participating in trial and principal investigators:
UK - 9 centres
St. Mary's London (Levin), Guy's (Murdoch), Great Ormond St. (Klein), Alder Hey Liverpool (Thomson), Newcastle (Hoare), Leicester (Nichani), Nottingham (Thomas), Stoke-on-Trent (Alexander), Sheffield (Finn).
USA - 16 centres
Colorado (Durmowicz), Wisconsin (Gedeit), San Diego (Bradley), Cook's (Shelton), Oregon (Goldstein), Dallas (Giroir), St. Joseph's (Sastry), Seattle (Martin), Oakland (Loeffler), Portland (Quint), Tulsa (Barton), Arkansas (Jacobs), Texas (Kaplan), University Community (Orlowski), Hosp for Sick Children (Shemie), Wisconsin (Zimmerman).
The adult trial of rBPI21 for severe meningococcaemia
A trial in adults has started at the Hammersmith Hospital using Ealing Hospital as a satellite site.
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