Clinical trial NCT00000963: A Study of Dideoxyinosine (ddI) in HIV-Infected Children Who Have Not Had Success With Zidovudine or Who Cannot Take Zidovudine
Official title: A Randomized Comparative Trial of Two Doses of 2',3'-Dideoxyinosine (ddI) in Children With Symptomatic HIV Infection Who Are Either Unresponsive to Zidovudine and/or Who Are Intolerant to Zidovudine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Didanosine
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
First posted: 2001-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To evaluate the effectiveness, safety, and tolerance of two doses of didanosine (ddI) in the treatment of children with symptomatic HIV disease who have had to discontinue zidovudine (AZT) because of intolerance and/or who have experienced progressive disease while on AZT.

The progression of immunodeficiency due to HIV infection can be delayed by using AZT. The benefits of AZT in adults with AIDS and severe AIDS-related complex (ARC) appear to last for approximately 12 to 18 months, at which time most patients have progressive deterioration. Recently published literature has described a reduced sensitivity of HIV isolated from patients after prolonged AZT treatment. Although the clinical significance of this is unclear, it makes the development of new antiretroviral drugs important.

Detailed description: The progression of immunodeficiency due to HIV infection can be delayed by using AZT. The benefits of AZT in adults with AIDS and severe AIDS-related complex (ARC) appear to last for approximately 12 to 18 months, at which time most patients have progressive deterioration. Recently published literature has described a reduced sensitivity of HIV isolated from patients after prolonged AZT treatment. Although the clinical significance of this is unclear, it makes the development of new antiretroviral drugs important.

Children who show AZT intolerance and/or progressive disease after 6 months of AZT therapy receive oral ddI at 1 of 2 doses for a minimum of 48 weeks, with a 48-week extension. Patients are seen for clinical and laboratory evaluations at scheduled times during the study. (Per 5/12/92 amendment, new patients will not be enrolled in the pharmacokinetics studies.) Per 10/31/94 amendment: Patients are eligible to receive blinded study drug for an additional 8-16 weeks after the final on-study visit, but no later than 2/15/95.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP).
* Immunoglobulin.
* Maintenance therapy with amphotericin B (l mg/kg) up to 5 days/week.

Concurrent Treatment:

Allowed:

* Blood transfusions.

Prior Medication:

Allowed:

* Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP).

Patients enrolled in ACTG 128 and ACTG 138 must meet study end points or meet protocol definitions for being permanently off zidovudine (AZT) before enrolling in this study.

* Patients currently enrolled in ACTG 051 who have not reached the study end points but who meet the entry criteria for ACTG 144 may be co-enrolled in ACTG 144.
* Patient or guardian available to give written informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded.

* Hypersensitivity to didanosine (ddI).
* Symptomatic cardiomyopathy.
* Seizures that are not well controlled by ongoing anticonvulsant therapy.
* Symptomatic pancreatitis.
* Grade 1 or higher peripheral neuropathy.
* Active malignancy requiring chemotherapy.

Concurrent Medication:

Excluded:

* Zidovudine (AZT), other antiretroviral agents, biological modifiers, and investigational medications.

Avoid:

* Drugs with potential to cause peripheral neuropathy or pancreatitis.

Patients with the following are excluded:

* Active malignancy requiring concomitant chemotherapy.

Prior Medication:

Excluded:

* Antiretroviral agents other than zidovudine (AZT) or dideoxycytidine (ddC) within 4 weeks of study entry.
* Immunomodulating agents such as interferons, isoprinosine, or interleukin-2 within 2 weeks of entry.
* Any other experimental therapy within 1 week of entry.
* Drugs that have or will cause prolonged neutropenia, significant pancreatitis, significant nephrotoxicity, or peripheral neuropathy within 1 week of entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Farmington
country: United States
facility: Univ. of Connecticut Health Ctr., Dept. of Ped.
state: Connecticut
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
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: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Atlanta
country: United States
facility: Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases
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 at Chicago, Dept. of Peds.
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 Med. Ctr. - Charity Hosp. of New Orleans, ACTU
state: Louisiana
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: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
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: Paterson
country: United States
facility: St. Joseph's Hosp. & Med. Ctr. of New Jersey
state: New Jersey
city: Albany
country: United States
facility: Children's Hospital at Albany Medical Center, Dept. of Peds.
state: New York
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: NYU Med. Ctr., Dept. of Medicine
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: Univ. of Rochester ACTG CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
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: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
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: Frenkel LM
role: STUDY_CHAIR
name: Bryson Y
role: STUDY_CHAIR
name: Stiehm R
role: STUDY_CHAIR
References:
citation: Carey VJ, Yong F, Frenkel L, McKinney R. Enhancing the prognostic value of bodily growth histories in HIV-positive pediatric cohorts. Int Conf AIDS. 1996 Jul 7-12;11(2):134 (abstract no WeC3444)
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.