Clinical trial NCT00002391: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV-1
Drug Therapy, Combination
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Child Development
abacavir
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ Alabama - Birmingham / Dept of Pediatrics / UAB Station
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hosp Los Angeles
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic Treatment Ctr
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida - Gainesville / Infectious Dis & Immun
state: Florida
city: Miami
country: United States
facility: Univ of Miami / Fox Cancer Research Ctr
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hosp for Women and Children
state: Florida
city: Riviera Beach
country: United States
facility: Pediatric Special Immunology Clinic / HRS / PBC PHU
state: Florida
city: Saint Petersburg
country: United States
facility: Univ of South Florida All Children's Hosp
state: Florida
city: Tampa
country: United States
facility: Dr Patricia Emmanuel
state: Florida
city: Chicago
country: United States
facility: Mt Sinai Hosp Med Ctr / Dept of Pediatrics
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ Med School
state: Louisiana
city: Minneapolis
country: United States
facility: Univ of Minnesota Med School
state: Minnesota
city: Newark
country: United States
facility: UMDNJ / Division of Allergy Immunology & Infectious Diseases
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr / Dept of Pediatrics
state: New York
city: Buffalo
country: United States
facility: PACT Program
state: New York
city: Great Neck
country: United States
facility: North Shore Univ Hosp / Pediatric Immunology
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp
state: New York
city: New York
country: United States
facility: New York Hosp - Cornell / Program for Children with AIDS
state: New York
city: New York
country: United States
facility: St Luke's - Roosevelt Hosp Ctr
state: New York
city: Stony Brook
country: United States
facility: SUNY Health Ctr at Stony Brook / Pediatric Infectious Dis
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Dept of Pediatrics
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina / Pediatric Infectious Diseases
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr / Pediatrics Dept / Infec Dis
state: North Carolina
city: Dayton
country: United States
facility: The Children's Med Ctr / Division of Infectious Dis
state: Ohio
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Children's Med Ctr of Dallas / ARMS Clinic
state: Texas
city: Fort Worth
country: United States
facility: Cook's Ft Worth Children Med Ctr / Pediatric Inf Dis
state: Texas
city: San Antonio
country: United States
facility: Univ of Texas Health Sciences Ctr
state: Texas
city: Norfolk
country: United States
facility: Eastern VA Med Sch / Children's Hosp of the King's Daughters
state: Virginia
Study officials:
References: