Clinical Trial of Safety and Efficacy of IHN-A21 for the Prevention of Nosocomial Staphylococcal Bloodstream Infection in Premature Infants

doi:10.1016/j.jpeds.2007.04.060

The Journal of Pediatrics

Volume 151, Issue 3, September 2007, Pages 260-265.e1

https://doi.org/10.1016/j.jpeds.2007.04.060 Get rights and content

Objective

To determine if INH-A21, an intravenous immune globulin (IGIV) derived from donors with high titers of antibody to surface adhesins of Staphylococcus epidermidis and S aureus prevents late-onset sepsis (LOS) in very low birth weight (VLBW) infants.

Study design

In this double-blind, placebo-controlled study, infants with birth weights 500 to 1250 g were randomized to receive up to four doses of INH-A21 (Veronate®) or placebo. The primary objective was to determine the safety and efficacy of INH-A21 versus placebo for prevention of S aureus LOS in VLBW infants.

Results

A total of 1983 infants from 95 neonatal intensive care units were randomized, and received at least one dose of study drug. S aureus LOS developed in 50 of 989 (5%) and 60 of 994 (6%) infants who received placebo or INH-A21, respectively (P = .34). No differences were found in the frequencies of LOS caused by coagulase-negative staphylococci (CoNS), Candida spp, or overall mortality. No adverse events were statistically significantly associated with INH-A21 infusions compared with placebo.

Conclusion

INH-A21 failed to reduce the incidence of staphylococcal LOS or candidemia in premature infants.

Section snippets

Patients and Eligibility

This clinical trial was conducted at 95 study centers in the United States and Canada between May 26, 2004 and January 21, 2006. Premature infants between postnatal days 3 to 5 (beginning at hour 49 and through hour 120 after delivery) were eligible for enrollment if they met the following criteria: birth weight ≥500 and ≤1250 g and expected to survive at least 4 weeks and to require intravenous access for 10 to 14 days. Infants were excluded if there was evidence of active sepsis (defined by

Subjects

From 95 neonatal intensive care units in the US and Canada, 2017 infants were enrolled. Thirty-four infants did not receive any infusion of study drug (INH-A21 or placebo), usually because they became clinically unstable, and were not included in the analysis (Figure 1). Among the 1983 infants enrolled who received at least one infusion of study drug, 989 and 994 received placebo and INH-A21, respectively. The mean and median ages at the time of the first infusion were 4.2 and 4.0 days, for

Discussion

The potential to prevent infection in a high-risk population of premature infants through administration of immune globulin has been attractive for several reasons. The neonate born before 32 weeks gestation is deficient in IgG. Specific antibody is believed to be a critical component of host defense against staphylococci, which represent the most common pathogens for LOS.17, 18, 19, 20

Multiple trials have attempted to reduce LOS by administration of IGIV.7, 10, 21, 22, 23 The meta-analysis by

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: This study is registered at www.clinicaltrials.gov; registration number = NCT00113191.

: The study was funded in its entirety by Inhibitex, Inc. A. Morris, B. Kapik, D. Roberson, J. Patti, and S. Hetherington were all employees of Inhibitex during the course of the study.

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Original articleClinical Trial of Safety and Efficacy of IHN-A21 for the Prevention of Nosocomial Staphylococcal Bloodstream Infection in Premature Infants

Objective

Study design

Results

Conclusion

Section snippets

Patients and Eligibility

Subjects

Discussion

Semin Perinatol

J Pediatr

J Pediatr

Am J Kidney Dis

Am J Kidney Dis

Births: final data for 2000

Natl Vital Stat Rep

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infantsThe National Institute of Child Health and Human Development Neonatal Research Network

Pediatr Infect Dis J

Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network

Pediatrics

Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection

JAMA

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infantsNational Institute of Child Health and Human Development Neonatal Research Network

N Engl J Med

Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants

Cochrane Database Syst Rev

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonatesThe Multicenter Group for the Study of Immune Globulin in Neonates

N Engl J Med

Features of invasive staphylococcal disease in neonates

Pediatrics

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

Pediatr Infect Dis J

Anti-clumping factor A immunoglobulin reduces the duration of methicillin-resistant Staphylococcus aureus bacteremia in an experimental model of infective endocarditis

Antimicrob Agents Chemother

MSCRAMM-mediated adherence of microorganisms to host tissues

Annu Rev Microbiol

Multicenter study to determine antibody concentrations and assess the safety of administration of INH-A21, a donor-selected human staphylococcal immune globulin, in low-birth-weight infants

Antimicrob Agents Chemother

Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma

Pediatr Res

Original article
Clinical Trial of Safety and Efficacy of IHN-A21 for the Prevention of Nosocomial Staphylococcal Bloodstream Infection in Premature Infants