Clinical trial NCT00000720: A Double-Blind, Placebo-Controlled Trial To Evaluate Intravenous Gamma Globulin in Children With Symptomatic HIV Infection Receiving Zidovudine
Official title: A Double-Blind, Placebo-Controlled Trial To Evaluate Intravenous Gamma Globulin in Children With Symptomatic HIV Infection Receiving Zidovudine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: AIDS-Related Opportunistic Infections
Placebos
Infusions, Intravenous
Gamma-Globulins
Combined Modality Therapy
Acquired Immunodeficiency Syndrome
Zidovudine
Bacterial Infections
Immunization, Passive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 250
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Downey
country: United States
facility: Kaiser Permanente / UCLA Med Ctr
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial (Pediatric)
state: California
city: Los Angeles
country: United States
facility: Children's Hosp of Los Angeles/UCLA Med Ctr
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai / UCLA Med Ctr
state: California
city: Los Angeles
country: United States
facility: Martin Luther King Jr Gen Hosp / UCLA Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr / Pediatric
state: California
city: Menlo Park
country: United States
facility: Stanford Univ School of Medicine
state: California
city: Oakland
country: United States
facility: Children's Hosp of Oakland
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: San Francisco
country: United States
facility: Northern California Pediatric AIDS Treatment Ctr / UCSF
state: California
city: Sylmar
country: United States
facility: Olive View Med Ctr
state: California
city: Farmington
country: United States
facility: Univ of Connecticut Health Ctr / Pediatrics
state: Connecticut
city: Atlanta
country: United States
facility: Emory Univ School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Illinois College of Medicine
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's Memorial Hosp
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Univ Med Ctr
state: Maryland
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Boston
country: United States
facility: Boston Med Ctr
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med Ctr
state: Massachusetts
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: Newark
country: United States
facility: Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
state: New Jersey
city: Bronx
country: United States
facility: Lincoln Hosp Ctr / Pediatrics
state: New York
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
state: New York
city: Elmhurst
country: United States
facility: City Hosp Ctr at Elmhurst / Mount Sinai Hosp
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp / Long Island Jewish Med Ctr
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr / Pediatrics
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Saint Luke's - Roosevelt Hosp Ctr
state: New York
city: New York
country: United States
facility: Metropolitan Hosp Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: New York
country: United States
facility: Columbia Univ Babies' Hosp
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Hosp / New York Med College / Pediatrics
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Holmes Hosp / Univ of Cincinnati Med Ctr
state: Ohio
city: Cleveland
country: United States
facility: Univ Hosp of Cleveland / Case Western Reserve Univ
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hosp
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Saint Christopher's Hosp for Children
state: Pennsylvania
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Houston
country: United States
facility: Hermann Hosp / Univ Texas Health Science Ctr
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: Seattle
country: United States
facility: Children's Hosp of Seattle
state: Washington
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
city: San Juan
country: Puerto Rico
facility: UPR Children's Hosp / San Juan City Hosp
Study officials:
name: Spector, SA
role: STUDY_CHAIR
References:
citation: Connor E, McSherry G. Treatment of HIV infection in infancy. Clin Perinatol. 1994 Mar;21(1):163-77.
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. doi: 10.1203/00006450-199305001-00464.
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.
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)
citation: 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.