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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000720

Collaborator

(none)

250

Enrollment

Locations

4.9

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Globulin, Immune Drug: Zidovudine	Phase 3

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 Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Apr 1, 1993

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente / UCLA Med Ctr	Downey	California	United States	902422814
2	Long Beach Memorial (Pediatric)	Long Beach	California	United States	90801
3	Children's Hosp of Los Angeles/UCLA Med Ctr	Los Angeles	California	United States	900276016
4	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
5	Cedars Sinai / UCLA Med Ctr	Los Angeles	California	United States	900481804
6	Martin Luther King Jr Gen Hosp / UCLA Med Ctr	Los Angeles	California	United States	900593019
7	UCLA Med Ctr / Pediatric	Los Angeles	California	United States	900951752
8	Stanford Univ School of Medicine	Menlo Park	California	United States	94025
9	Children's Hosp of Oakland	Oakland	California	United States	946091809
10	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
11	Northern California Pediatric AIDS Treatment Ctr / UCSF	San Francisco	California	United States	94143
12	Olive View Med Ctr	Sylmar	California	United States	91342
13	Univ of Connecticut Health Ctr / Pediatrics	Farmington	Connecticut	United States	06032
14	Emory Univ School of Medicine	Atlanta	Georgia	United States	30303
15	Cook County Hosp	Chicago	Illinois	United States	60612
16	Univ of Illinois College of Medicine	Chicago	Illinois	United States	60612
17	Chicago Children's Memorial Hosp	Chicago	Illinois	United States	606143394
18	Tulane Univ School of Medicine	New Orleans	Louisiana	United States	70112
19	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland	United States	21201
20	Children's Hosp of Boston	Boston	Massachusetts	United States	021155724
21	Boston Med Ctr	Boston	Massachusetts	United States	02118
22	Univ of Massachusetts Med Ctr	Worcester	Massachusetts	United States	01655
23	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
24	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey	United States	071072198
25	Lincoln Hosp Ctr / Pediatrics	Bronx	New York	United States	10451
26	Albert Einstein College of Medicine	Bronx	New York	United States	10461
27	SUNY / Health Sciences Ctr at Brooklyn / Pediatrics	Brooklyn	New York	United States	11203
28	City Hosp Ctr at Elmhurst / Mount Sinai Hosp	Elmhurst	New York	United States	11373
29	Schneider Children's Hosp / Long Island Jewish Med Ctr	New Hyde Park	New York	United States	11042
30	Beth Israel Med Ctr / Pediatrics	New York	New York	United States	10003
31	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
32	Saint Luke's - Roosevelt Hosp Ctr	New York	New York	United States	10025
33	Metropolitan Hosp Ctr	New York	New York	United States	10029
34	Mount Sinai Med Ctr	New York	New York	United States	10029
35	Columbia Univ Babies' Hosp	New York	New York	United States	10032
36	Harlem Hosp Ctr	New York	New York	United States	10037
37	Univ of Rochester Medical Center	Rochester	New York	United States	14642
38	Westchester Hosp / New York Med College / Pediatrics	Valhalla	New York	United States	10595
39	Duke Univ Med Ctr	Durham	North Carolina	United States	277103499
40	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio	United States	452670405
41	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio	United States	44106
42	Columbus Children's Hosp	Columbus	Ohio	United States	432052696
43	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
44	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania	United States	191341095
45	Julio Arroyo	West Columbia	South Carolina	United States	29169
46	Hermann Hosp / Univ Texas Health Science Ctr	Houston	Texas	United States	77030
47	Texas Children's Hosp / Baylor Univ	Houston	Texas	United States	77030
48	Children's Hosp of Seattle	Seattle	Washington	United States	98105
49	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon		Puerto Rico	00619
50	San Juan City Hosp	San Juan		Puerto Rico	009367344
51	UPR Children's Hosp / San Juan City Hosp	San Juan		Puerto Rico	00936