The Safety and Effectiveness of Zidovudine Plus Lamivudine, Used With and Without 1592U89, in HIV-1 Infected Children Who Have Taken Anti-HIV-1 Drugs

Sponsor

Glaxo Wellcome (Industry)

Overall Status

Completed

CT.gov ID

NCT00002391

Collaborator

(none)

Locations

Study Details

Study Description

Brief Summary

To compare the safety, tolerance, durability of the viral load response and the antiviral activity of the 1592U89/zidovudine(ZDV)/lamivudine (3TC) regimen vs. ZDV/3TC regimen. To determine the clinical efficacy of the two regimens as measured survival, disease progression, weight growth velocity, and neuropsychological or neurological changes. To assess the development of viral resistance and relative pharmacokinetics associated with each regimen.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Abacavir sulfate Drug: Lamivudine Drug: Zidovudine	Phase 3

Detailed Description

Patients are randomized to receive blinded treatment with ZDV/3TC alone or in combination with 1592U89, orally for 16 weeks. If after the 16-week period certain criteria are met, patients may have the option to switch to open-label treatment for the remainder of the study period.

Study Design

Study Type:

Interventional

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

A Double-Blind, Randomized, Multicenter Trial to Evaluate the Safety and Efficacy of the Combination of 1592U89/Zidovudine (ZDV)/Lamivudine (3TC) Versus the Combination of Zidovudine (ZDV)/Lamivudine (3TC) in HIV-1 Therapy-Experienced Pediatric Patients.

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:

Intravenous immunoglobulin G, erythropoietin, G-CSF and GM-CSF.
Opportunistic infection prophylaxis.

Patients must have:

HIV-1 infection documented by:

< 18 months of age:

one positive viral test culture and one other positive viral test (culture, PCR, p24 antigen, or Immune Complex Dissociation p24 antigen) on two different specimens.

= 18 months of age:

two positive viral tests as stated above, one or both of which may be determined by a federally documented ELISA and confirmed by Western blot or Indirect Fluorescent Antibody test.
Any of the CDC Categories:
1, 2, 3, and N, A, B, and C of the 1994 Revised Classification System for HIV Infection in Children Less than 13 Years of Age.
CD4+ count >= 15% within 14 days prior to study drug administration.
No active or ongoing AIDS-defining opportunistic infection that precludes absorption of study drug or observation of a study parameter.
Signed, informed consent from parent or legal guardian for patients under 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

Serious bacterial infection that precludes absorption of study drug or observation of a study parameter.
Documented hypersensitivity to a nucleoside analog.
Co-enrollment in certain opportunistic infection protocols is not exclusionary if approval is obtained.
Malignancy.
Life-threatening infection or other chronic disease that may compromise patient safety.
Grade 3/4 clinical or laboratory toxicity or current grade 2 or higher pancreatic amylase or lipase toxicity as defined by the ACTG Toxicity Tables within 14 days prior to study entry.

Concurrent Medication:

Excluded:

Other anti-HIV therapy.
Probenecid.
Biologic response modifier (unless listed under included concurrent medication) and megestrol acetate.
Human growth hormone.
Immunomodulators and cytotoxic chemotherapeutic agents.
Systemic corticosteroids > 14 days without approval.
Investigational agents.

Concurrent Treatment:

Excluded:

Radiation therapy.

Patients with the following prior conditions are excluded:

History of clinically relevant pancreatitis or hepatitis within the past 6 months.
Participation in a vaccine trial.

Prior Medication:

Excluded:

Protease inhibitor therapy within 2 weeks prior to randomization.
Interleukins or interferons within 30 days prior to study drug administration.
Investigational drugs within 14 days prior to randomization.
HIV vaccine dose within past 30 days.

Required:

12 weeks prior antiretroviral therapy and unchanged therapy 12 weeks prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ Alabama - Birmingham / Dept of Pediatrics / UAB Station	Birmingham	Alabama	United States	35294
2	Children's Hosp Los Angeles	Los Angeles	California	United States	90027
3	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
4	Children's Diagnostic Treatment Ctr	Fort Lauderdale	Florida	United States	33301
5	Univ of Florida - Gainesville / Infectious Dis & Immun	Gainesville	Florida	United States	326100296
6	Univ of Miami / Fox Cancer Research Ctr	Miami	Florida	United States	33136
7	Arnold Palmer Hosp for Women and Children	Orlando	Florida	United States	32806
8	Pediatric Special Immunology Clinic / HRS / PBC PHU	Riviera Beach	Florida	United States	33404
9	Univ of South Florida All Children's Hosp	Saint Petersburg	Florida	United States	33701
10	Dr Patricia Emmanuel	Tampa	Florida	United States	33606
11	Mt Sinai Hosp Med Ctr / Dept of Pediatrics	Chicago	Illinois	United States	60608
12	Tulane Univ Med School	New Orleans	Louisiana	United States	70112
13	Univ of Minnesota Med School	Minneapolis	Minnesota	United States	55455
14	UMDNJ / Division of Allergy Immunology & Infectious Diseases	Newark	New Jersey	United States	07103
15	Bronx Lebanon Hosp Ctr / Dept of Pediatrics	Bronx	New York	United States	10457
16	PACT Program	Buffalo	New York	United States	14222
17	North Shore Univ Hosp / Pediatric Immunology	Great Neck	New York	United States	11021
18	Schneider Children's Hosp	New Hyde Park	New York	United States	11040
19	New York Hosp - Cornell / Program for Children with AIDS	New York	New York	United States	10021
20	St Luke's - Roosevelt Hosp Ctr	New York	New York	United States	10025
21	SUNY Health Ctr at Stony Brook / Pediatric Infectious Dis	Stony Brook	New York	United States	117948111
22	SUNY Health Sciences Ctr at Syracuse / Dept of Pediatrics	Syracuse	New York	United States	13210
23	Univ of North Carolina / Pediatric Infectious Diseases	Chapel Hill	North Carolina	United States	27514
24	Duke Univ Med Ctr / Pediatrics Dept / Infec Dis	Durham	North Carolina	United States	27710
25	The Children's Med Ctr / Division of Infectious Dis	Dayton	Ohio	United States	454041815
26	Med Univ of South Carolina	Charleston	South Carolina	United States	294253312
27	Children's Med Ctr of Dallas / ARMS Clinic	Dallas	Texas	United States	75235
28	Cook's Ft Worth Children Med Ctr / Pediatric Inf Dis	Fort Worth	Texas	United States	76104
29	Univ of Texas Health Sciences Ctr	San Antonio	Texas	United States	78284
30	Eastern VA Med Sch / Children's Hosp of the King's Daughters	Norfolk	Virginia	United States	23507