title: Multicenter study to assess safety and efficacy of INH-A21, a donor-selected human staphylococcal immunoglobulin, for prevention of nosocomial infections in very low birth weight infants.
abstract: BACKGROUND
  Prophylactic administration of intravenous immunoglobulin has been inconsistent in reducing the risk of sepsis in very low birth weight (VLBW) infants presumably because of varying titers of organism specific IgG antibodies. INH-A21 is an intravenous immunoglobulin from donors with high titers of antistaphylococcal antibodies. This dose-ranging study explored safety and preliminary activity of INH-A21 for prevention of staphylococcal sepsis in VLBW infants.
  
  
  METHODS
  This was a multicenter, double blind, group-sequential study. Infants with birth weights 500-1250 g were randomized to receive up to 4 doses of placebo, 250 mg/kg, 500 mg/kg or 750 mg/kg INH-A21. Safety and frequencies of sepsis were compared across treatment groups.
  
  
  RESULTS
  All treatment groups had similar mean gestational age, birth weight, Apgar score and maternal use of antibiotics. Randomizations to 250 mg/kg (N = 94) and 500 mg/kg (N = 96) doses were terminated after interim analyses demonstrated a low probability of finding a difference when compared with placebo. Infants randomized to the INH-A21 750 mg/kg group (N = 157) had fewer episodes of Staphylococcus aureus sepsis [relative risk (RR), 0.37; 95% confidence interval (CI), 0.12-1.12; P = 0.14], candidemia (RR 0.34; 95% CI 0.09-1.22; P = 0.09) and mortality (RR 0.64; 95% CI 0.25-1.61; P = 0.27) when compared with the placebo-treated cohort (N = 158). No dose-related trends were observed for adverse events or morbidities associated with prematurity.
  
  
  CONCLUSIONS
  INH-A21 750 mg/kg demonstrated potential to reduce sepsis caused by S. aureus, candidemia and mortality in VLBW infants. Although statistical significance was not reached, based on the magnitude of the estimated differences, the efficacy and safety of INH-A21 750 mg/kg should be evaluated in an adequately powered, well-controlled study.
authors.affiliation: Wesley Medical Center, Wichita, KS, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Bloom
authors.forename: Robert
authors.initials: R
authors.lastname: Schelonka
authors.forename: Tom
authors.initials: T
authors.lastname: Kueser
authors.forename: Whit
authors.initials: W
authors.lastname: Walker
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jung
authors.forename: David
authors.initials: D
authors.lastname: Kaufman
authors.forename: Karen
authors.initials: K
authors.lastname: Kesler
authors.forename: Destrey
authors.initials: D
authors.lastname: Roberson
authors.forename: Joseph
authors.initials: J
authors.lastname: Patti
authors.forename: Seth
authors.initials: S
authors.lastname: Hetherington
mesh_terms: D003428:Cross Infection / Q000401:mortality / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D008297:Male; D018805:Sepsis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013210:Staphylococcus / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous