A Double-Blind, Placebo-Controlled Trial To Evaluate Intravenous Gamma Globulin in Children With Symptomatic HIV Infection Receiving Zidovudine

To evaluate the clinical, immunologic, and virologic effects of oral zidovudine (AZT) plus intravenous immunoglobulin (IVIG) versus AZT plus placebo (albumin). It is estimated that by 1991, there may be 10,000 to 20,000 HIV-infected children in the United States. HIV infection in children is most often associated with symptomatic disease and poor prognosis. Treatment with antiviral therapy may be effective in changing the course of disease and decreasing mortality in this vulnerable population. AZT treatment has been shown to decrease mortality and the frequency of opportunistic infections in certain adult AIDS patients; therefore, it is likely that children may also benefit from this antiviral therapy. In addition, bacterial infections are frequently found in HIV-infected children. Because pooled human serum immunoglobulin, another name for antibodies, is effective in reducing bacterial infection in patients with defects of immunity, it may reduce the rate of bacterial infection in HIV-infected children as well. In this study, AZT will be administered together with IVIG to determine safety, tolerance, and efficacy of the combined treatment.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Globulin, Immune

Detailed Description

It is estimated that by 1991, there may be 10,000 to 20,000 HIV-infected children in the United States. HIV infection in children is most often associated with symptomatic disease and poor prognosis. Treatment with antiviral therapy may be effective in changing the course of disease and decreasing mortality in this vulnerable population. AZT treatment has been shown to decrease mortality and the frequency of opportunistic infections in certain adult AIDS patients; therefore, it is likely that children may also benefit from this antiviral therapy. In addition, bacterial infections are frequently found in HIV-infected children. Because pooled human serum immunoglobulin, another name for antibodies, is effective in reducing bacterial infection in patients with defects of immunity, it may reduce the rate of bacterial infection in HIV-infected children as well. In this study, AZT will be administered together with IVIG to determine safety, tolerance, and efficacy of the combined treatment.

The study includes 250 children, 3 months to 12 years of age. All participants receive oral AZT. IVIG or intravenous placebo is administered every 28 days. Patients are followed for the development of serious bacterial infection, as well as for a number of factors relating to safety, tolerance, progression of disease, and survival. This is an outpatient study conducted over a minimum 100-week period. The children are evaluated every 2 weeks for the first 8 weeks, and monthly thereafter.

• Study Type: Interventional
• Enrollment: 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamon, Puerto Rico, 00619
    • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • San Juan, Puerto Rico, 009367344
    • San Juan City Hosp
  • San Juan, Puerto Rico, 00936
    • UPR Children's Hosp / San Juan City Hosp
• United States
  • California
    • Downey, California, United States, 902422814
      • Kaiser Permanente / UCLA Med Ctr
    • Long Beach, California, United States, 90801
      • Long Beach Memorial (Pediatric)
    • Los Angeles, California, United States, 900276016
      • Children's Hosp of Los Angeles/UCLA Med Ctr
    • Los Angeles, California, United States, 90033
      • Los Angeles County - USC Med Ctr
    • Los Angeles, California, United States, 900481804
      • Cedars Sinai / UCLA Med Ctr
    • Los Angeles, California, United States, 900951752
      • UCLA Med Ctr / Pediatric
    • Los Angeles, California, United States, 900593019
      • Martin Luther King Jr Gen Hosp / UCLA Med Ctr
    • Menlo Park, California, United States, 94025
      • Stanford Univ School of Medicine
    • Oakland, California, United States, 946091809
      • Children's Hosp of Oakland
    • San Diego, California, United States, 921036325
      • Univ of California / San Diego Treatment Ctr
    • San Francisco, California, United States, 94143
      • Northern California Pediatric AIDS Treatment Ctr / UCSF
    • Sylmar, California, United States, 91342
      • Olive View Med Ctr
  • Connecticut
    • Farmington, Connecticut, United States, 06032
      • Univ of Connecticut Health Ctr / Pediatrics
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory Univ School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
    • Chicago, Illinois, United States, 606143394
      • Chicago Children's Memorial Hosp
    • Chicago, Illinois, United States, 60612
      • Univ of Illinois College of Medicine
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ of Maryland at Baltimore / Univ Med Ctr
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Med Ctr
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
    • Worcester, Massachusetts, United States, 01655
      • Univ of Massachusetts Med Ctr
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Univ of Minnesota
  • New Jersey
    • Newark, New Jersey, United States, 071072198
      • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine
    • Bronx, New York, United States, 10451
      • Lincoln Hosp Ctr / Pediatrics
    • Brooklyn, New York, United States, 11203
      • SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
    • Elmhurst, New York, United States, 11373
      • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
    • New Hyde Park, New York, United States, 11042
      • Schneider Children's Hosp / Long Island Jewish Med Ctr
    • New York, New York, United States, 10016
      • Bellevue Hosp / New York Univ Med Ctr
    • New York, New York, United States, 10025
      • Saint Luke's - Roosevelt Hosp Ctr
    • New York, New York, United States, 10029
      • Mount Sinai Med Ctr
    • New York, New York, United States, 10029
      • Metropolitan Hosp Ctr
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
    • New York, New York, United States, 10003
      • Beth Israel Med Ctr / Pediatrics
    • New York, New York, United States, 10032
      • Columbia Univ Babies' Hosp
    • Rochester, New York, United States, 14642
      • Univ of Rochester Medical Center
    • Valhalla, New York, United States, 10595
      • Westchester Hosp / New York Med College / Pediatrics
  • North Carolina
    • Durham, North Carolina, United States, 277103499
      • Duke Univ Med Ctr
  • Ohio
    • Cincinnati, Ohio, United States, 452670405
      • Holmes Hosp / Univ of Cincinnati Med Ctr
    • Cleveland, Ohio, United States, 44106
      • Univ Hosp of Cleveland / Case Western Reserve Univ
    • Columbus, Ohio, United States, 432101228
      • Ohio State Univ Hosp Clinic
    • Columbus, Ohio, United States, 432052696
      • Columbus Children's Hosp
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 191341095
      • Saint Christopher's Hosp for Children
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Julio Arroyo
  • Texas
    • Houston, Texas, United States, 77030
      • Hermann Hosp / Univ Texas Health Science Ctr
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp / Baylor Univ
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hosp of Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Benadryl and/or acetaminophen may be given before and during intravenous immunoglobulin (IVIG) infusion in patients demonstrating mild reactions during infusion.
• Acetaminophen for short-term fever and pain.
• Zidovudine (AZT).
• Steroids.
• Oral or systemic (swish and swallow) nystatin.
• Maintenance therapy for fungal disease or tuberculosis.
• Prophylaxis for a previous episode of Pneumocystis carinii pneumonia (PCP) including the use of trimethoprim / sulfamethoxazole (TMP / SMX). The dosage is specified as TMP 75 mg/m2 twice daily 3 times a week and SMX 375 mg/m2 twice daily 3 times a week.
• Recommended:
• Children with AIDS and / or CD4 count = or < 500 cells/mm3 should receive primary PCP prophylaxis as described.

Concurrent Treatment:

Allowed:

• Blood transfusion for hemoglobin < 8 g/dl and hematocrit < 24 percent or bone marrow suppression.
• Supplemental oxygen with a prestudy PaO2 < 70 mmHg.

Children must have one or more of the indicator diseases of AIDS; however, there must be an absence of acute opportunistic infection and an absence of bacterial infection requiring treatment at the time of entry into the study.

• Children with lymphoid interstitial proliferation (LIP) are excluded from enrollment unless they have had additional AIDS-defining opportunistic infections, meet ARC criteria, have had two or more serious bacterial infections in the 12 months prior to study entry, have evidence of HIV encephalopathy, or are currently on supplemental oxygen and steroids with a pre-treatment PaO2 < 70 mm Hg.
• Children with concurrent LIP and ARC are eligible for inclusion. Thrombocytopenia is an exclusion except if it is HIV-associated.
• Children randomized prior to their 13th birthday are eligible.
• All lab values must be within 4 weeks of study entry.

Prior Medication:

Allowed:

• Zidovudine (AZT).

Exclusion Criteria

Co-existing Condition:

Patients with the following will be excluded:

• Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection.
• Known hypersensitivity to immunoglobulin.
• Active HIV thrombocytopenia requiring IVIG therapy.

Concurrent Medication:

Excluded:

• Chronic acetaminophen.
• Drugs that are metabolized by hepatic glucuronidation should not be used for more than 24 hours without notifying the study physician.
• Antibacterial prophylaxis for otitis, sinusitis, or urinary tract infection.
• Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP) prior to the first episode of laboratory-documented PCP.
• Immunoglobulin (IVIG) therapy required for active HIV thrombocytopenia.

Patients with the following will be excluded:

• Lymphoid interstitial proliferation (LIP) not requiring steroids and supplemental oxygen or with other lymphoproliferative diseases as their sole clinical evidence of HIV infection.
• Known hypersensitivity to immunoglobulin.
• Active HIV thrombocytopenia requiring IVIG therapy.
• Inability to establish or maintain intravenous access.
• Lack of parental or guardian authorization for intravenous access.

Prior Medication:

Excluded within 4 weeks of study entry:

• Any other experimental therapy.
• Other antiretroviral agents.
• Drugs which cause prolonged neutropenia or significant nephrotoxicity.
• Immunoglobulins.
• Immunomodulating agents.

Active alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Spector, SA

Publications and helpful links

General Publications

• Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7.
• Spector SA, Gelber RD, McGrath N, Wara D, Barzilai A, Abrams E, Bryson YJ, Dankner WM, Livingston RA, Connor EM. A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group. N Engl J Med. 1994 Nov 3;331(18):1181-7. doi: 10.1056/NEJM199411033311802.
• Connor E, McSherry G. Treatment of HIV infection in infancy. Clin Perinatol. 1994 Mar;21(1):163-77.
• Mofenson LM, Moye J Jr. Intravenous immune globulin for the prevention of infections in children with symptomatic human immunodeficiency virus infection. Pediatr Res. 1993 Jan;33(1 Suppl):S80-7; discussion S87-9. doi: 10.1203/00006450-199305001-00464.
• Spector SA, Gelber RD, McGrath N, Connor EM, Wara DW, Balsley JF. Results of a double-blind placebo-controlled trial to evaluate intravenous gamma globulin in children with symptomatic HIV infection receiving zidovudine (ACTG 051). The Pediatric AIDS Clinical Trials Group and the NICHD Pediatric HIV Centers. Int Conf AIDS. 1993 Jun 6-11;9(1):48 (abstract no WS-B05-6)

Study record dates

Study Major Dates

• Study Completion (Actual): April 1, 1993

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Bacterial Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Zidovudine; Placebos; Combined Modality Therapy; Infusions, Intravenous; Immunization, Passive; Gamma-Globulins
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Immunologic Factors; Antibodies; Immunoglobulins; Zidovudine
• Other Study ID Numbers: ACTG 051; 11025 (DAIDS ES Registry Number)