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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000720
• Other study ID #: ACTG 051
• Secondary ID: 11025
• Status: Completed
• Phase: Phase 3
• Est. completion date: April 1993

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: April 1993
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections

Intervention

Drug:
• Globulin, Immune

• Zidovudine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	UPR Children's Hosp / San Juan City Hosp	San Juan
United States	Emory Univ School of Medicine	Atlanta	Georgia
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Boston Med Ctr	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Lincoln Hosp Ctr / Pediatrics	Bronx	New York
United States	SUNY / Health Sciences Ctr at Brooklyn / Pediatrics	Brooklyn	New York
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine	Chicago	Illinois
United States	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio
United States	Columbus Children's Hosp	Columbus	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Kaiser Permanente / UCLA Med Ctr	Downey	California
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York
United States	Univ of Connecticut Health Ctr / Pediatrics	Farmington	Connecticut
United States	Hermann Hosp / Univ Texas Health Science Ctr	Houston	Texas
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Long Beach Memorial (Pediatric)	Long Beach	California
United States	Cedars Sinai / UCLA Med Ctr	Los Angeles	California
United States	Children's Hosp of Los Angeles/UCLA Med Ctr	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Martin Luther King Jr Gen Hosp / UCLA Med Ctr	Los Angeles	California
United States	UCLA Med Ctr / Pediatric	Los Angeles	California
United States	Stanford Univ School of Medicine	Menlo Park	California
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Schneider Children's Hosp / Long Island Jewish Med Ctr	New Hyde Park	New York
United States	Tulane Univ School of Medicine	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Pediatrics	New York	New York
United States	Columbia Univ Babies' Hosp	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Metropolitan Hosp Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Saint Luke's - Roosevelt Hosp Ctr	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	Children's Hosp of Oakland	Oakland	California
United States	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	Northern California Pediatric AIDS Treatment Ctr / UCSF	San Francisco	California
United States	Children's Hosp of Seattle	Seattle	Washington
United States	Olive View Med Ctr	Sylmar	California
United States	Westchester Hosp / New York Med College / Pediatrics	Valhalla	New York
United States	Julio Arroyo	West Columbia	South Carolina
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

Connor E, McSherry G. Treatment of HIV infection in infancy. Clin Perinatol. 1994 Mar;21(1):163-77. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation