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A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT00000833
Collaborator
(none)
20
Enrollment
15
Locations
1.3
Patients Per Site

Study Details

Study Description

Brief Summary

To compare the safety, toxicity, and tolerance of two doses of ribavirin in combination with didanosine (ddI) to HIV-infected children. To determine the toxicity of ddI/ribavirin and compare it to the expected toxicity of ddI monotherapy. To determine the effect of concurrent ribavirin on the pharmacokinetics of ddI. To determine a dosage of ribavirin that would be suitable for a Phase II/III evaluation of ddI/ribavirin.

Ribavirin, a broad spectrum antiviral agent, may enhance the antiretroviral activity of didanosine ( ddI ) without a concomitant increase in toxicity. Ribavirin alters the intracellular metabolism of ddI, enhancing the antiretroviral activity of the active form of ddI.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Ribavirin, a broad spectrum antiviral agent, may enhance the antiretroviral activity of didanosine ( ddI ) without a concomitant increase in toxicity. Ribavirin alters the intracellular metabolism of ddI, enhancing the antiretroviral activity of the active form of ddI.

Patients are divided into two cohorts. Subjects will be stratified by age 3 months to < 24 months and >= 24 months to 12 years. Fifty % of patients from each age group will be assigned to each cohort. Cohort 1 receives ddI monotherapy for 4 weeks, followed by combination ddl/ribavirin therapy for an additional 20 weeks. Cohort 2 receives combination ddI/ribavirin for 24 weeks. In both cohorts, after study medications are stopped, patients are treated with prescription antiretrovirals for 4 more weeks. [AS PER AMENDMENT 7/2/96: Note: In each cohort of 10 subjects at least 2 of 5 children from the older half of the cohort will have an ICD p24 antigen at entry.]

Study Design

Study Type:
Interventional
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.
Actual Study Completion Date :
Jul 1, 1998

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Months to 12 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    Concurrent Medication:
    Recommended:
    • PCP prophylaxis.
    Allowed:

    • Acetaminophen for no more than 72 hours.

    • Immunoglobulin.

    • Corticosteroids.

    • Erythropoietin.

    • G-CSF and GM-CSF.

    • Ethionamide or isoniazid for TB if no alternative available.

    • Immunizations according to current recommendations.

    Patients must have:

    • HIV infection.

    • Immunologic abnormality or clinical symptoms as detailed in the Disease Status field.

    • No active AIDS-defining opportunistic infection or malignancy, no progressive encephalopathy attributable to HIV and no chronic persistent diarrhea.

    • Consent of parent or guardian.

    PER AMENDMENT 7/2/96:
    • At least 2 of the 5 children in the older half of each cohort must have an ICD p24 antigen concentration >= 70 pg/ml at screening.
    Prior Medication:
    Allowed:

    • Up to 6 weeks of prior immunomodulator therapy.

    • Maternal immunomodulator or antiretroviral therapy, including during pregnancy.

    • Prior corticosteroids or intravenous immunoglobulin.

    Exclusion Criteria

    Co-existing Condition:
    Patients with the following symptoms or conditions are excluded:

    • Current grade 3 or worse neuropathy/lower motor neuropathy.

    • Clinical or laboratory grade 3 or worse toxicities.

    • Active serious bacterial infection.

    Concurrent Medication:
    Excluded:

    • Chemotherapy for active malignancy.

    • Antiretrovirals other than study drugs.

    • Immunomodulators unless specifically allowed.

    Patients with the following prior condition are excluded:
    • History of grade 3 or worse neuropathy/lower motor neuropathy.
    Prior Medication:
    Excluded:

    • Prior ddI or oral ribavirin.

    • Aerosolized ribavirin within 6 weeks prior to study entry.

    • Antiretroviral or immunomodulator therapy (other than corticosteroids or IVIG) within 1 week prior to blood draws for study entry.

    Ongoing drug or alcohol abuse.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hosp of Washington DC Washington District of Columbia United States 200102916
    2 Howard Univ Hosp Washington District of Columbia United States 20060
    3 Univ of Florida Health Science Ctr / Pediatrics Jacksonville Florida United States 32209
    4 Tulane Univ / Charity Hosp of New Orleans New Orleans Louisiana United States 701122699
    5 Children's Hosp of Boston Boston Massachusetts United States 021155724
    6 Univ of Medicine & Dentistry of New Jersey / Univ Hosp Newark New Jersey United States 071032714
    7 Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl Newark New Jersey United States 071072198
    8 Bronx Lebanon Hosp Ctr Bronx New York United States 10457
    9 Schneider Children's Hosp New Hyde Park New York United States 11040
    10 Columbia Presbyterian Med Ctr New York New York United States 10032
    11 Incarnation Children's Ctr / Columbia Presbyterian Med Ctr New York New York United States 10032
    12 Harlem Hosp Ctr New York New York United States 10037
    13 Glaxo Wellcome Inc Research Triangle Park North Carolina United States 27709
    14 Texas Children's Hosp / Baylor Univ Houston Texas United States 77030
    15 Univ of Puerto Rico / Univ Children's Hosp AIDS San Juan Puerto Rico 009365067

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)

    Investigators

    • Study Chair: Van Dyke R,
    • Study Chair: McSherry G,

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT00000833
    Other Study ID Numbers:
    • ACTG 274
    • 11250
    First Posted:
    Aug 31, 2001
    Last Update Posted:
    Oct 28, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
    Ribavirin
    Didanosine
    Drug Therapy, Combination
    Acquired Immunodeficiency Syndrome
    AIDS-Related Complex
    Antiviral Agents
    Additional relevant MeSH terms:
    HIV Infections
    Ribavirin
    Didanosine

    Study Results

    No Results Posted as of Oct 28, 2021