Intravenous Immune Globulin (IVIG) to Prevent Neonatal Infection (IVIG)

Randomized Clinical Trial of Intravenous Immune Globulin (IVIG) to Prevent Neonatal Infection in Very-Low-Birth-Weight Infants

A controlled clinical trial was conducted at eight participating centers between January 1, 1988, and March 31, 1991. Patients were randomly assigned to an intravenous immune globulin group or a control group. There were two phases to the study (see below). During phase 1 the control infants received infusions of placebo. During phase 2 the control infants received no infusion therapy.

Study Overview

• Status: Completed
• Conditions: Sepsis; Infant, Small for Gestational Age; Infant, Premature; Infant, Low Birth Weight; Infant, Newborn
• Intervention / Treatment: Drug: IVIG; Drug: Placebo

Detailed Description

Although survival rates for very-low-birth-weight infants (≤ 1.5 kg) continue to increase, nosocomial infections remain a major cause of morbidity and mortality. Prolonged hospitalization with exposure to resistant organisms and multiple invasive procedures, in the presence of immunologic immaturity, renders these infants vulnerable to hospital-acquired infections. Prior studies testing the ability of intravenous immune globulin to prevent nosocomial infections in premature infants have varied in design and sample size. Despite differences in the rates of observed infection, immune globulin preparations, doses, and infusion intervals, a meta-analysis of published reports suggests that nosocomial infections may be diminished by the prophylactic infusion of IgG.

The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network therefore performed a prospective, multicenter, randomized trial at eight participating centers to test the hypothesis that the intravenous administration of immune globulin to infants with birth weights between 501 and 1500g would reduce the incidence of nosocomial infections.

Patients were randomly assigned to an intravenous immune globulin group or a control group. During phase 1 the control infants received infusions of placebo. During phase 2 the control infants received no infusion therapy.

• Study Type: Interventional
• Enrollment (Actual): 2416
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • District of Columbia
    • Washington, District of Columbia, United States, 20052
      • George Washington University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center at Dallas
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All neonates with birth weights of 501 to 1500 g

Exclusion Criteria:

• More than 72 hours old
• One of three or more fetuses from a multiple pregnancy
• Had infections associated with toxoplasma, rubella, cytomegalovirus, and herpes simplex viruses (the TORCH complex)
• Has a major congenital malformation, an identifiable syndrome, or a chromosomal abnormality
• Were considered nonviable
• Parental consent could not be obtained

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immune globulin; Lyophilized human immune globulin product	Drug: IVIG; The infants received their first dose of study drug within 24 hours of randomization.; Other Names: Sandoglobulin
Placebo Comparator: Albumin solution	Drug: Placebo; An equal volume of 5 percent albumin solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of nosocomial infection	Including septicemia, meningitis, or urinary tract infection	120 days of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death		120 Days of life
Morbidity	Duration of ventilator support, frequency of bronchopulmonary dysplasia, and duration of hospitalization	120 days of life
Local infections		120 days of life
Necrotizing enterocolitis		120 days of life
Specific complications of immune globulin or placebo infusion		120 days of life

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Investigators: Study Director: Avroy A. Fanaroff, MD, Case Western Reserve University; Principal Investigator: Ronald L. Poland, MD, Wayne State University; Principal Investigator: Joseph B. Philips, MD, University of Alabama at Birmingham; Principal Investigator: Jerold F. Lucey, MD, University of Vermont, Burlington

Publications and helpful links

General Publications

• Fanaroff AA, Korones SB, Wright LL, Verter J, Poland RL, Bauer CR, Tyson JE, Philips JB 3rd, Edwards W, Lucey JF, Catz CS, Shankaran S, Oh W. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J. 1998 Jul;17(7):593-8. doi: 10.1097/00006454-199807000-00004.
• Fanaroff AA, Korones SB, Wright LL, Wright EC, Poland RL, Bauer CB, Tyson JE, Philips JB 3rd, Edwards W, Lucey JF, et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1994 Apr 21;330(16):1107-13. doi: 10.1056/NEJM199404213301602.

Helpful Links

• NICHD Neonatal Research Network

Study record dates

Study Major Dates

• Study Start: January 1, 1988
• Primary Completion (Actual): March 1, 1991
• Study Completion (Actual): March 1, 1991

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Actual): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Meningitis; Prematurity; Urinary tract infection; NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Septicemia; Immune globulin
• Additional Relevant MeSH Terms: Body Weight; Infections; Birth Weight; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: NICHD-NRN-0002; U10HD021364 (U.S. NIH Grant/Contract); U10HD021373 (U.S. NIH Grant/Contract); U10HD021385 (U.S. NIH Grant/Contract); U01HD019897 (U.S. NIH Grant/Contract); U10HD021415 (U.S. NIH Grant/Contract); U10HD021397 (U.S. NIH Grant/Contract)