Clinical trial NCT00000814: A Comparative Study of Combination Antiretroviral Therapy in Children and Adolescents With Advanced HIV Disease
Official title: A Comparative Study of Combination Antiretroviral Therapy in Children and Adolescents With Advanced HIV Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Nevirapine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 390
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To compare the antiviral activity, safety, toxicity, and steady-state pharmacokinetics of zidovudine, didanosine, and nevirapine used in combination in patients with HIV infection.

The duration of clinical benefit from zidovudine (AZT) may be limited because of development of viral resistance to the drug. Use of combination antiretroviral therapy can potentially reduce viral load and prevent emergence of multidrug resistance.

Detailed description: The duration of clinical benefit from zidovudine (AZT) may be limited because of development of viral resistance to the drug. Use of combination antiretroviral therapy can potentially reduce viral load and prevent emergence of multidrug resistance.

In Stage 1 of the study, a minimum of 22 patients are randomized to each of three treatment arms: didanosine (ddI) plus AZT plus nevirapine (NVP); ddI plus AZT; and ddI plus NVP. After 12 weeks of treatment, the study proceeds to Stage 2 provided at least 40 percent of patients in Stage 1 show a reduction of at least 40 percent from baseline ICD p24 antigen of greater than or equal to 70 pg/ml AND fewer than two patients experience grade 4 rash. Patients in Stage 1 continue treatment for an additional 36 weeks. In Stage 2, additional patients are randomized to each original treatment regimen until a maximum of 130 patients per arm have been entered. Stage 2 patients receive treatment for at least 48 weeks.

AS PER AMENDMENT 02/12/97: As of 2/28/97, patients receiving study drugs will be offered blinded study drugs for an additional 16 weeks (until 6/30/97). Patients will be unblinded on or about 5/23/97.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Erythropoietin.

Concurrent Treatment:

Allowed:

* Transfusion.

Patients must have:

* Progressive HIV disease.
* At least 24 weeks prior cumulative nucleoside analog antiretroviral monotherapy or combination therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Active malignancy requiring chemotherapy.
* Currently receiving therapy in an ACTG primary therapy or salvage protocol who have NOT met an endpoint on that study.
* Known intolerance (other than hematologic) or toxicity to ddI, AZT, or NVP at the doses used in this study.

Concurrent Medication:

Excluded (unless exemption made by study chair):

* Oral anticoagulants (warfarin, dicumarol).
* Oral contraceptives.
* Digitalis glycosides.
* Phenytoin.
* Theophylline.

Patients with the following prior conditions are excluded:

* History of clinical pancreatitis.
* History of grade 2 or worse peripheral neuropathy.

Prior Treatment:

Excluded:

* Acute treatment for a serious bacterial, viral, or opportunistic infection 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: 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: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai / UCLA 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: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
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: Georgetown Univ Med Ctr
state: District of Columbia
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: 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: 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: 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: 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: New Brunswick
country: United States
facility: UMDNJ - Robert Wood Johnson Med School / Pediatrics
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: 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: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr / 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: 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: Cornell Univ Med College
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 / Hemophilia Treatment 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: 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: 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: Columbus
country: United States
facility: Columbus Children's Hosp
state: Ohio
city: Dayton
country: United States
facility: West Central Ohio Hemophilia Ctr / Children's Med Ctr
state: Ohio
city: Hershey
country: United States
facility: Milton S Hershey Med Ctr
state: Pennsylvania
city: Hershey
country: United States
facility: Univ of Pittsburgh Med School / Hershey Med Ctr
state: Pennsylvania
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: Dallas
country: United States
facility: Children's Med Ctr of Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp of the King's Daughters
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: 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: Burchett S
role: STUDY_CHAIR
name: Luzuriaga K
role: STUDY_CHAIR
References:
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: Burchett SK, Carey V, Yong F, Sullivan J, Sulzbacher S, Civitello L, Culnane M, Mofenson L, Siminski S, Robinson P, Luzuriaga K. Virologic activity of didanosine (ddI), zidovudine (ZDV) and nevirapine (NVP) combinations in pediatric subjects with advanced HIV disease (ACTG 245). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:130 (abstract no 271)
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: Burchett S, Sullivan J, Luzuriaga K, Carey V, Yong F, Culnane M, Mofenson L, Robinson P. Combinations of didanosine (DDI), zidovudine (ZDV) and nevirapine (NVP) can reduce CSF HIV-1 viral load in pediatric patients with advanced HIV disease. Int Conf AIDS. 1998;12:62 (abstract no 12253)