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

Barry Bloom, Robert Schelonka, Tom Kueser, Whit Walker, Elizabeth Jung, David Kaufman, Karen Kesler, Destrey Roberson, Joseph Patti, Seth Hetherington

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalPediatric Infectious Disease Journal
Volume24
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

Fingerprint

Very Low Birth Weight Infant
Cross Infection
Multicenter Studies
Immunoglobulins
Tissue Donors
Sepsis
Safety
Candidemia
Intravenous Immunoglobulins
Placebos
Confidence Intervals
Birth Weight
Staphylococcus aureus
Apgar Score
Mortality
Antibodies
Random Allocation
Gestational Age
Veronate
Immunoglobulin G

Keywords

  • Antistaphylococcal IgG
  • INH-A21
  • Nosocomial infections
  • Premature infants
  • Sepsis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)

Cite this

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. / Bloom, Barry; Schelonka, Robert; Kueser, Tom; Walker, Whit; Jung, Elizabeth; Kaufman, David; Kesler, Karen; Roberson, Destrey; Patti, Joseph; Hetherington, Seth.

In: Pediatric Infectious Disease Journal, Vol. 24, No. 10, 10.2005, p. 858-866.

Research output: Contribution to journalArticle

Bloom, Barry ; Schelonka, Robert ; Kueser, Tom ; Walker, Whit ; Jung, Elizabeth ; Kaufman, David ; Kesler, Karen ; Roberson, Destrey ; Patti, Joseph ; Hetherington, Seth. / 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. In: Pediatric Infectious Disease Journal. 2005 ; Vol. 24, No. 10. pp. 858-866.
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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.",
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T1 - 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

AU - Bloom, Barry

AU - Schelonka, Robert

AU - Kueser, Tom

AU - Walker, Whit

AU - Jung, Elizabeth

AU - Kaufman, David

AU - Kesler, Karen

AU - Roberson, Destrey

AU - Patti, Joseph

AU - Hetherington, Seth

PY - 2005/10

Y1 - 2005/10

N2 - 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.

AB - 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.

KW - Antistaphylococcal IgG

KW - INH-A21

KW - Nosocomial infections

KW - Premature infants

KW - Sepsis

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