Clinical trial NCT00001066: A Comparison of Zidovudine Plus Lamivudine Versus ddI Used Alone or in Combination With Zidovudine in HIV-1 Infected Children
Official title: A Randomized Comparative Study of Combined Zidovudine-Lamivudine (3TC) vs. the Better of ddI Monotherapy vs. Zidovudine Plus Ddl in Symptomatic HIV-1 Infected Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lamivudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 740
Sex: ALL
Minimum age (years): 3
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To compare the efficacy of lamivudine (3TC) and zidovudine (AZT) in combination versus the better of didanosine (ddI) monotherapy or ddI/AZT combination, in symptomatic HIV-1 infected children who received less than 56 days of prior antiretroviral therapy. To evaluate the safety and tolerance of 3TC/AZT in this patient population. To determine other measures of diseases in response to the study regimens.

Currently, none of the potential treatments for HIV-1 infection has proven to be both nontoxic and effective in long-term use. However, previous studies in both adults and children have shown that 3TC combined with AZT reduced HIV load in blood and increased white blood cells. Additionally, 3TC has demonstrated a favorable safety profile.

Detailed description: Currently, none of the potential treatments for HIV-1 infection has proven to be both nontoxic and effective in long-term use. However, previous studies in both adults and children have shown that 3TC combined with AZT reduced HIV load in blood and increased white blood cells. Additionally, 3TC has demonstrated a favorable safety profile.

Patients are randomized to receive oral 3TC/AZT, ddI/AZT, or ddI alone for at least 24 months. PER AMENDMENT 4/29/96: NOTE: Randomization to ZDV+ddI arm was terminated in Spring of 1996 based upon the results of ACTG 152. Patients on that arm will continue on blinded study drug and will be followed until the end of the study.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* IVIG.
* Prophylaxis for opportunistic infection.
* EPO.
* G-CSF or GM-CSF.

Patients must have:

* Symptomatic HIV infection.
* Less than 56 days of prior antiretroviral therapy.
* Consent of parent or guardian.

NOTE:

* Co-enrollment on ACTG 219, ACTG 220, and certain ACTG opportunistic infection protocols is permitted.

Prior Medication:

Allowed:

* Up to 56 days of prior antiretroviral therapy.
* Prior immunomodulator therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Malignancy.
* Hypersensitivity to a nucleoside analog.
* Current grade 2 or higher amylase/lipase toxicity or grade 3 or 4 other toxicity.

PER AMENDMENT 4/29/96:

* Active opportunistic infection and/or serious bacterial infection at the time of entry.

Concurrent Medication:

Excluded:

* Any other anti-HIV therapy.
* Megestrol acetate ( Megace ).
* Probenecid.
* IV pentamidine.
* Human growth hormone ( hGH ).
* Systemic corticosteroids for more than 2 weeks.

Prior Medication:

Excluded:

* Investigational drug therapy within 14 days prior to study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham Schl of Med / Pediatrics
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hosp
state: Arkansas
city: La Jolla
country: United States
facility: UCSD Med Ctr / Pediatrics / Clinical Sciences
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: UCLA Med Ctr / Pediatric
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: Sacramento
country: United States
facility: Univ of California / Davis
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Stanford
country: United States
facility: Stanford Univ School of Medicine
state: California
city: Denver
country: United States
facility: Children's Hosp of Denver
state: Colorado
city: Farmington
country: United States
facility: Univ of Connecticut / Farmington
state: Connecticut
city: New Haven
country: United States
facility: Yale Univ Med School
state: Connecticut
city: Washington
country: United States
facility: Children's Hosp of Washington DC
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic and Treatment Ctr of South Florida
state: Florida
city: Gainesville
country: United States
facility: Univ of Florida
state: Florida
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hosp for Children & Women
state: Florida
city: St Petersburg
country: United States
facility: All Children's Hosp
state: Florida
city: Tampa
country: United States
facility: Univ of South Florida
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hosp
state: Florida
city: West Palm Beach
country: United States
facility: HRS Palm Beach County Public Health Unit
state: Florida
city: Atlanta
country: United States
facility: Emory Univ Hosp / Pediatrics
state: Georgia
city: Augusta
country: United States
facility: Med College of Georgia
state: Georgia
city: Savannah
country: United States
facility: Mem Children's Hosp
state: Georgia
city: Chicago
country: United States
facility: Mount Sinai Hosp Med Ctr
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: Chicago
country: United States
facility: Univ of Illinois College of Medicine / Pediatrics
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: 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: Boston
country: United States
facility: Boston City Hosp / Pediatrics
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: Minneapolis
country: United States
facility: Univ of Minnesota Med School
state: Minnesota
city: Jackson
country: United States
facility: Univ of Mississippi Med Ctr
state: Mississippi
city: St Louis
country: United States
facility: St Louis Children's Hosp
state: Missouri
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson Med School / Pediatrics
state: New Jersey
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: Newark
country: United States
facility: Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
state: New Jersey
city: Albany
country: United States
facility: Children's Hosp at Albany Med Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Brooklyn
country: United States
facility: King's County Hosp Ctr / Pediatrics
state: New York
city: Brooklyn
country: United States
facility: SUNY - Brooklyn
state: New York
city: Buffalo
country: United States
facility: Children's Hosp of Buffalo
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: 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 / Pediatrics
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
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: 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: Valhalla
country: United States
facility: Westchester Hosp
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Durham
country: United States
facility: Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hosp / Univ Hosp
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve Univ - Pediatric
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hosp
state: Ohio
city: Dayton
country: United States
facility: Children's Med Ctr
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hosp of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hosp for Children
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hosp / Brown Univ
state: Rhode Island
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Univ of South Carolina School of Med
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: Fort Worth
country: United States
facility: Cook - Fort Worth Children's Med Ctr
state: Texas
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: San Antonio
country: United States
facility: Univ of Texas Health Science Ctr
state: Texas
city: Norfolk
country: United States
facility: Senetara Norfolk Gen Hosp
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth Univ
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: Mayaguez
country: Puerto Rico
facility: Mayaguez Med Ctr
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: McKinney RE
role: STUDY_CHAIR
name: Johnson GM
role: STUDY_CHAIR
References:
citation: Combination therapies improve outlook for children with HIV disease. NIAID AIDS Agenda. 1997 Aug:10.
citation: McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173
citation: James JS. Major pediatric study stopped early: combination treatment better. AIDS Treat News. 1997 Jul 4;(No 274):5-6.
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: Benjamin DK Jr, Miller WC, Benjamin DK, Ryder RW, Weber DJ, Walter E, McKinney RE. A comparison of height and weight velocity as a part of the composite endpoint in pediatric HIV. AIDS. 2003 Nov 7;17(16):2331-6. doi: 10.1097/00002030-200311070-00007.