Clinical trial NCT00000851: Comparison of Stavudine Used Alone or in Combination With Didanosine in HIV-Infected Children
Official title: Trial of Stavudine (d4T) Plus Didanosine (ddI) in Children on Long-Term Stavudine Monotherapy, and Stavudine Versus Stavudine Plus Didanosine in Children on Long-Term Zidovudine Monotherapy: A Rollover Protocol for ACTG 240 Participants and Children Receiving Prescription Zidovudine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Didanosine
Drug Therapy, Combination
Antiviral Agents
Stavudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 198
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and determine the pharmacokinetic disposition of stavudine (d4T) alone and in combination with didanosine (ddI), and whether concurrent administration alters the disposition of either drug. To compare d4T versus d4T plus ddI with respect to short and long term changes from baseline in plasma HIV RNA concentrations. To determine the relationship, if any, between drug exposure and viral burden.

In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

Detailed description: In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

Eligible subjects receiving d4T will be assigned in an open manner to Arm 1, and subjects who have been receiving zidovudine (AZT) will be assigned in a randomized, double blind manner to Arms 2 and 3. Each subject will receive study drug for 48 weeks as follows: Arm 1 - d4T plus ddI, Arm 2 - d4T alone, Arm 3 - d4T plus ddI.

Eligibility criteria: Inclusion Criteria

Patients must:

* Be on-study, on-treatment in ACTG 240, or receiving AZT monotherapy by prescription for at least 6 months immediately preceding enrollment.
* Have laboratory evidence of HIV-1 infection \< 18 months - 2 positive viral tests \>= 18 months - 2 positive viral tests or 2 or more positive tests for HIV antibody
* Have parent or legal guardian willing to sign a consent.

Prior Medication: Required:

* On-study, on-treatment in ACTG 240 (D4T or AZT) or receiving AZT monotherapy by prescription for at least six months immediately preceding this trial.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

* Intractable diarrhea or vomiting.
* Current clinical or laboratory Grade 3 or worse toxicities.

Concurrent Medication:

Excluded:

* Concurrent use of antiretroviral agents other than those provided by the study, immunomodulators (other than IVIG or corticosteroids), or other investigational drugs except for those in ACTG 254 and ACTG 219.
* Chemotherapy for active malignancy.

Patients with any of the following prior conditions are excluded:

* Reached an ACTG 240 defined endpoint, or are permanently off ACTG 240 study treatment.
* Prescription AZT recipients may not have received \> 6 weeks of d4T or ddI previously.
* Subjects who have had chemotherapy for active malignancy.

Prior Medication:

Excluded:

* Prescription AZT recipients may not have received \> 6 weeks of d4T or ddI previously.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Farmington
country: United States
facility: Univ. of Connecticut Health Ctr., Dept. of Ped.
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Med. Ctr.
state: Connecticut
city: Washington
country: United States
facility: Children's National Med. Ctr., ACTU
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ. Washington DC NICHD CRS
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Cook County Hosp.
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan NICHD CRS
state: Michigan
city: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson
state: New Jersey
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
state: New York
city: Great Neck
country: United States
facility: North Shore-Long Island Jewish Health System, Dept. of Peds.
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hosp., Div. of Infectious Diseases
state: New York
city: New York
country: United States
facility: Metropolitan Hosp. NICHD CRS
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: St. Christopher's Hosp. for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases
state: South Carolina
city: Dallas
country: United States
facility: Children's Med. Ctr. Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Bayamon
country: Puerto Rico
facility: Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
name: Kline M
role: STUDY_CHAIR
name: Van Dyke R
role: STUDY_CHAIR
References:
citation: Kline MW, Van Dyke RB, Lindsey JC, Gwynne M, Culnane M, Diaz C, Yogev R, McKinney RE Jr, Abrams EJ, Mofenson LM. Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. The Pediatric AIDS Clinical Trials Group 327 Team. Pediatrics. 1999 May;103(5):e62. doi: 10.1542/peds.103.5.e62.
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.