Clinical trial NCT00000924: A Study to Compare Two Different Anti-HIV Drug Regimens
Official title: A Phase II Randomized, Multicenter Protocol Evaluating Two Antiretroviral Regimens Containing Combinations of Protease Inhibitors, NRTIs, and an NNRTI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 4
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: This study compares 2 different anti-HIV drug regimens to determine which is the most effective in lowering the amount of HIV in the blood. The anti-HIV drugs used in this study are 2 protease inhibitors (nelfinavir and ritonavir), 2 nucleoside reverse transcriptase inhibitors (stavudine and didanosine), and 1 nonnucleoside reverse transcriptase inhibitor (nevirapine).

These drug combinations have been previously studied in adults, but there is limited information on how well they work in HIV-infected children. It is important to develop drug combinations which are effective at suppressing the HIV virus in children.

Detailed description: The use of combination therapy with 2 or more antiretroviral agents has been strongly supported by recent studies in both children and adults. However, as of yet, few combinations of antiretrovirals have been studied in large cohorts of stable HIV-1 infected, antiretroviral-experienced children. Evidence suggests that viral suppression may be more difficult to achieve in children. Therefore, it is important to develop new drug combinations which can maximally suppress plasma HIV-1 RNA concentrations in children.

Patients are stratified by prior antiretroviral treatment (zidovudine \[ZDV\]/lamivudine \[3TC\] versus d4T/other treatment) and by age (under 24 months versus 24 months and older). Patients are then randomized to 1 of 4 treatment groups.

Arm A1: ddI/NFV/RTV (for prior ZDV/3TC-treated patients). Arm A2: ddI/NFV/RTV (for prior d4T/other-treated patients). Arm B1: d4T/NFV/NVP (for prior ZDV/3TC-treated patients). Arm B2: d4T/NFV/NVP (for prior d4T/other-treated patients). Treatment is administered for 48 weeks. At Weeks 2, 4, and then every 4 weeks thereafter, patients undergo physical examinations, and blood samples are drawn to measure viral load. \[AS PER AMENDMENT 4/27/00: Patients in Arms A1 and A2 may continue to receive medication for an additional 24 weeks. While on the treatment extension, patients must continue their current schedule for study drug administration and completion of study visits. Patients in Arms A1 and A2 who have reached Week 44 participate in an enteric-coated ddI pharmacokinetic study as part of this 24-week extension. Patients who were enrolled in Arms A1 or A2 and who were taken off study after reaching Week 48 may be re-entered onto the study at Week 52 regardless of the number of weeks they have been off study.\]

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are between 4 months and 21 years of age (consent of parent or guardian required if under 18).
* Are HIV-positive.
* Have a viral level of at least 4,000 copies/ml.
* Have a CD4 cell count of at least 750 (under 12 months of age), at least 500 (1 to 5 years of age), or at least 200 (6 years of age or older) cells/mm3 within the past 4 months or a CD4 percent of 15 percent or higher within the past 4 months.
* Have received the same continuous antiretroviral therapy for the past 16 weeks.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have an active opportunistic and/or serious bacterial infection.
* Have been diagnosed with a malignancy.
* Have received prior treatment with certain antiretroviral medications.
* Are pregnant or breast-feeding.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham - Pediatric
state: Alabama
city: Mobile
country: United States
facility: Univ of South Alabama
state: Alabama
city: Long Beach
country: United States
facility: Long Beach Memorial (Pediatric)
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: Harbor - UCLA Med Ctr / UCLA School of Medicine
state: California
city: Oakland
country: United States
facility: Children's Hosp of Oakland
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: North Broward Hosp District
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida Gainesville
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Atlanta
country: United States
facility: Emory Univ Hosp / Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's Memorial Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Chicago Children's Hosp
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ / Charity Hosp of New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Earl K Long Early Intervention Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Univ Med Ctr
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp - Pediatric
state: Maryland
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hosp of Michigan
state: Michigan
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Newark
country: United States
facility: Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Great Neck
country: United States
facility: North Shore Univ Hosp
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: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Metropolitan Hosp Ctr
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
state: New York
city: New York
country: United States
facility: Harlem Hosp Ctr
state: New York
city: Stony Brook
country: United States
facility: State Univ of New York at Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Pediatrics
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Saint Jude Children's Research Hosp of Memphis
state: Tennessee
city: Dallas
country: United States
facility: Children's Med Ctr of Dallas
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Med College of Virginia
state: Virginia
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: Andrew Wiznia
role: STUDY_CHAIR
References:
citation: King JR, Nachman S, Yogev R, Hodge J, Aldrovandi G, Hughes MD, Chen J, Wiznia A, Damle B, Acosta EP. Efficacy, tolerability and pharmacokinetics of two nelfinavir-based regimens in human immunodeficiency virus-infected children and adolescents: pediatric AIDS clinical trials group protocol 403. Pediatr Infect Dis J. 2005 Oct;24(10):880-5. doi: 10.1097/01.inf.0000180508.21918.8a.