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

• ClinicalTrials.gov Identifier: NCT01203345
• Recruitment Status: Completed
• First Posted: September 16, 2010
• Last Update Posted: March 22, 2019
• Sponsor: NICHD Neonatal Research Network
• Information provided by: NICHD Neonatal Research Network

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infant, Newborn; Infant, Low Birth Weight; Infant, Small for Gestational Age; Infant, Premature; Sepsis	Drug: IVIG; Drug: Placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2416 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Clinical Trial of Intravenous Immune Globulin (IVIG) to Prevent Neonatal Infection in Very-Low-Birth-Weight Infants
• Study Start Date: January 1988
• Actual Primary Completion Date: March 1991
• Actual Study Completion Date: March 1991

Arms and Interventions

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 Name: Sandoglobulin
Placebo Comparator: Albumin solution	Drug: Placebo; An equal volume of 5 percent albumin solution

Outcome Measures

Primary Outcome Measures :

1. Incidence of nosocomial infection [ Time Frame: 120 days of life ]
   Including septicemia, meningitis, or urinary tract infection

Secondary Outcome Measures :

1. Death [ Time Frame: 120 Days of life ]
2. Morbidity [ Time Frame: 120 days of life ]
   Duration of ventilator support, frequency of bronchopulmonary dysplasia, and duration of hospitalization
3. Local infections [ Time Frame: 120 days of life ]
4. Necrotizing enterocolitis [ Time Frame: 120 days of life ]
5. Specific complications of immune globulin or placebo infusion [ Time Frame: 120 days of life ]

Eligibility Criteria

• Ages Eligible for Study: up to 72 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, District of Columbia

George Washington University

Washington, District of Columbia, United States, 20052

United States, Florida

University of Miami

Miami, Florida, United States, 33136

United States, Michigan

Wayne State University

Detroit, Michigan, United States, 48201

United States, Ohio

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States, 44106

United States, Tennessee

University of Tennessee

Memphis, Tennessee, United States, 38163

United States, Texas

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States, 75235

United States, Vermont

University of Vermont

Burlington, Vermont, United States, 05405

Sponsors and Collaborators

NICHD Neonatal Research Network

Investigators

• Study Director: Avroy A. Fanaroff, MD; Case Western Reserve University
• Principal Investigator: Sheldon B. Korones, MD; University of Tennessee
• Principal Investigator: Elizabeth C. Wright, PhD; George Washington University
• Principal Investigator: Ronald L. Poland, MD; Wayne State University
• Principal Investigator: Charles R. Bauer, MD; University of Miami
• Principal Investigator: Jon E. Tyson, MD MPH; University of Texas
• Principal Investigator: Joseph B. Philips, MD; University of Alabama at Birmingham
• Principal Investigator: Jerold F. Lucey, MD; University of Vermont, Burlington

More Information

Additional Information:

NICHD Neonatal Research Network 

Publications of Results:

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.

• Responsible Party: Avroy A. Fanaroff, Lead Principal Investigator, Case Western Reserve University
• ClinicalTrials.gov Identifier: NCT01203345
• Other Study ID Numbers: NICHD-NRN-0002; U10HD021364 ( U.S. NIH Grant/Contract ); U10HD021415 ( U.S. NIH Grant/Contract ); U01HD019897 ( U.S. NIH Grant/Contract ); U10HD021385 ( U.S. NIH Grant/Contract ); U10HD021397 ( U.S. NIH Grant/Contract ); U10HD021373 ( U.S. NIH Grant/Contract )
• First Posted: September 16, 2010
• Last Update Posted: March 22, 2019
• Last Verified: September 2010

Keywords provided by NICHD Neonatal Research Network:

NICHD Neonatal Research Network; Extremely Low Birth Weight (ELBW); Prematurity; Septicemia; Meningitis; Urinary tract infection; Immune globulin

Additional relevant MeSH terms:

Infections; Birth Weight; Body Weight; Immunoglobulins, Intravenous; Immunologic Factors; Physiological Effects of Drugs