Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis

Lancet. 1997 Nov 15;350(9089):1439-43. doi: 10.1016/s0140-6736(97)06468-4.


Background: Meningococcal sepsis remains an important cause of morbidity and mortality. We hypothesised that children with severe meningococcaemia might benefit from inhibition of the inflammatory processes thought responsible for fulminant disease. rBPI21 is a recombinant, N-terminal fragment of human bactericidal/permeability-increasing protein, which kills meningococci and binds to and clears bacterial endotoxin, these being the primary inducers of the systemic inflammation. The aim of this study was to determine the safety and kinetics of rBPI21 in children with severe meningococcaemia and to make a preliminary assessment of clinical outcome.

Methods: In this open-label, dose-escalation, phase I/II trial in severe meningococcaemia (Glasgow meningococcal prognostic septicaemia score [GMSPS] > or = 8), 26 patients aged 1-18 years, who had received their first dose of antibiotics no more than 8 hours earlier were given rBPI21 by infusion at total doses of 1.0, 2.0, and 4.0 mg/kg.

Findings: The patients had significantly raised plasma concentrations of bacterial endotoxin and cytokines. Peak and steady state BPI concentrations were comparable with pharmacokinetic data in healthy adults. All complications were compatible with the expected pattern for severe meningococcal sepsis. Only one patient died. This outcome was found to compare favourably with a predicted mortality of > or = 30% by GMSPS, > or = 15% by plasma endotoxin values, > or = 28% by plasma interleukin-6 concentrations, 29-49% by severity of coagulopathy, and 20% (11/54) by comparison with recent historical patients consecutively treated in participating centres before this study.

Interpretation: This, the first clinical trial or rBPI21, shows that rBPI21 can be safely administered to children with severe meningococcaemia and that the pharmacokinetics are consistent with patterns seen in healthy adults. Predicted mortality, on the basis of GMSPS, laboratory indices of inflammation and coagulopathy, and historical controls, was for between four and eight deaths. These findings have prompted a phase III randomised trial.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / therapeutic use*
  • Antimicrobial Cationic Peptides
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Blood Bactericidal Activity
  • Blood Proteins / adverse effects
  • Blood Proteins / pharmacokinetics
  • Blood Proteins / therapeutic use*
  • Child
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Membrane Proteins*
  • Meningococcal Infections / drug therapy*
  • Meningococcal Infections / mortality
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome


  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • bactericidal permeability increasing protein