A Study of Dideoxyinosine (ddI) in HIV-Infected Children Who Have Not Had Success With Zidovudine or Who Cannot Take Zidovudine

Condition(s) targeted: HIV Infections

Intervention: Didanosine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Frenkel LM, Study Chair
Bryson Y, Study Chair
Stiehm R, Study Chair

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.

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 design: Treatment

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.

Minimum age: 3 Months. Maximum age: 18 Years. Gender(s): Both.

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.

San Juan City Hosp, San Juan 009367344, Puerto Rico

UPR Children's Hosp / UPR School of Medicine, San Juan 009365067, Puerto Rico

Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico

Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, Puerto Rico

Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham, Alabama 35294, United States

UCSF / Moffitt Hosp - Pediatric, San Francisco, California 941430105, United States

UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States

Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles, California 905022004, United States

Children's Hosp of Oakland, Oakland, California 946091809, United States

UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States

Cedars Sinai / UCLA Med Ctr, Los Angeles, California 900481804, United States

Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States

Long Beach Memorial (Pediatric), Long Beach, California 90801, United States

Children's Hosp of Denver, Denver, Colorado 802181088, United States

Univ of Connecticut Health Ctr, Farmington, Connecticut 06032, United States

Yale Univ Med School, New Haven, Connecticut 06504, United States

Connecticut Children's Med Ctr, Farmington, Connecticut 060303805, United States

Children's Hosp of Washington DC / Children's Natl Med Ctr, Washington, District of Columbia 20010, United States

Howard Univ Hosp, Washington, District of Columbia 20060, United States

Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States

Georgetown Univ Med Ctr, Washington, District of Columbia 200072197, United States

Univ of Miami (Pediatric), Miami, Florida 33161, United States

Emory Univ Hosp / Pediatrics, Atlanta, Georgia 30306, United States

Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Univ of Illinois College of Medicine / Pediatrics, Chicago, Illinois 60612, United States

Univ of Chicago Children's Hosp, Chicago, Illinois 606371470, United States

Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States

Johns Hopkins Hosp - Pediatric, Baltimore, Maryland 212874933, United States

Children's Hosp of Boston, Boston, Massachusetts 021155724, United States

Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States

Univ of Massachusetts Med Ctr, Worcester, Massachusetts 01655, United States

Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States

Children's Hosp of Michigan, Detroit, Michigan 48201, United States

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark, New Jersey 07103, United States

Harlem Hosp Ctr, New York, New York 10037, United States

SUNY - Brooklyn, Brooklyn, New York 11203, United States

Cornell Univ Med College, New York, New York 10021, United States

North Shore Univ Hosp, Great Neck, New York 11021, United States

Westchester Hosp, Valhalla, New York 10595, United States

Schneider Children's Hosp, New Hyde Park, New York 11040, United States

Bronx Lebanon Hosp Ctr / Pediatrics, Bronx, New York 10457, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Columbia Presbyterian Med Ctr, New York, New York 10032, United States

Mount Sinai Med Ctr / Pediatrics, New York, New York 10029, United States

Albert Einstein College of Medicine, Bronx, New York 10461, United States

Metropolitan Hosp Ctr, New York, New York 10029, United States

Children's Hosp at Albany Med Ctr, Albany, New York 12208, United States

SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States

Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York, New York 10032, United States

SUNY / Health Sciences Ctr at Brooklyn / Pediatrics, Brooklyn, New York 11203, United States

State Univ of New York at Stony Brook, Stony Brook, New York 117948111, United States

Beth Israel Med Ctr / Pediatrics, New York, New York 10003, United States

Duke Univ Med Ctr, Durham, North Carolina 277103499, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Cincinnati Children's Hosp / Univ Hosp, Cincinnati, Ohio 452292899, United States

Columbus Children's Hosp, Columbus, Ohio 432052696, United States

Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States

Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States

Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States

Med Univ of South Carolina, Charleston, South Carolina 29425, United States

Children's Med Ctr of Dallas, Dallas, Texas 75235, United States

Hermann Hosp / Univ Texas Health Science Ctr, Houston, Texas 77030, United States

Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States

Children's Hosp of Seattle, Seattle, Washington 98105, United States

Click here for more information about Didanosine

Related publications:

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)

Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8.

Last updated: June 23, 2005