A Double-Blind, Placebo-Controlled Trial To Evaluate Intravenous Gamma Globulin in Children With Symptomatic HIV Infection Receiving Zidovudine
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on March 21, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Globulin, Immune (Drug); Zidovudine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Spector, SA, Study Chair
Summary
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.
Clinical Details
Official title: A Double-Blind, Placebo-Controlled Trial To Evaluate Intravenous Gamma Globulin in Children With Symptomatic HIV Infection Receiving Zidovudine
Study design: Treatment, Double-Blind
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.
Eligibility
Minimum age: 3 Months.
Maximum age: 12 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
San Juan City Hosp, San Juan 009367344, Puerto Rico
UPR Children's Hosp / San Juan City Hosp, San Juan 00936, Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00619, Puerto Rico
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Children's Hosp of Oakland, Oakland, California 946091809, United States
Kaiser Permanente / UCLA Med Ctr, Downey, California 902422814, United States
UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States
Children's Hosp of Los Angeles/UCLA Med Ctr, Los Angeles, California 900276016, United States
Cedars Sinai / UCLA Med Ctr, Los Angeles, California 900481804, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Martin Luther King Jr Gen Hosp / UCLA Med Ctr, Los Angeles, California 900593019, United States
Long Beach Memorial (Pediatric), Long Beach, California 90801, United States
Stanford Univ School of Medicine, Menlo Park, California 94025, United States
Northern California Pediatric AIDS Treatment Ctr / UCSF, San Francisco, California 94143, United States
Olive View Med Ctr, Sylmar, California 91342, United States
Univ of Connecticut Health Ctr / Pediatrics, Farmington, Connecticut 06032, United States
Emory Univ School of Medicine, Atlanta, Georgia 30303, United States
Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Illinois College of Medicine, Chicago, Illinois 60612, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Albert Einstein College of Medicine, Bronx, New York 10461, United States
Metropolitan Hosp Ctr, New York, New York 10029, United States
Saint Luke's - Roosevelt Hosp Ctr, New York, New York 10025, United States
Columbia Univ Babies' Hosp, New York, New York 10032, United States
Lincoln Hosp Ctr / Pediatrics, Bronx, New York 10451, United States
SUNY / Health Sciences Ctr at Brooklyn / Pediatrics, Brooklyn, New York 11203, United States
Westchester Hosp / New York Med College / Pediatrics, Valhalla, New York 10595, United States
Schneider Children's Hosp / Long Island Jewish Med Ctr, New Hyde Park, New York 11042, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States
Beth Israel Med Ctr / Pediatrics, New York, New York 10003, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Columbus Children's Hosp, Columbus, Ohio 432052696, United States
Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States
Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Hermann Hosp / Univ Texas Health Science Ctr, Houston, Texas 77030, United States
Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States
Children's Hosp of Seattle, Seattle, Washington 98105, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Globulin, Immune
Related publications: Connor E, McSherry G. Treatment of HIV infection in infancy. Clin Perinatol. 1994 Mar;21(1):163-77. Review. 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. Review. Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8. 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) 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.
Last updated: June 23, 2005
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