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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Didanosine; Drug: Ribavirin

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 Type: Interventional
• Enrollment: 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 009365067
    • Univ of Puerto Rico / Univ Children's Hosp AIDS
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 200102916
      • Children's Hosp of Washington DC
    • Washington, District of Columbia, United States, 20060
      • Howard Univ Hosp
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ of Florida Health Science Ctr / Pediatrics
  • Louisiana
    • New Orleans, Louisiana, United States, 701122699
      • Tulane Univ / Charity Hosp of New Orleans
  • Massachusetts
    • Boston, Massachusetts, United States, 021155724
      • Children's Hosp of Boston
  • New Jersey
    • Newark, New Jersey, United States, 071032714
      • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
    • Newark, New Jersey, United States, 071072198
      • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
  • New York
    • Bronx, New York, United States, 10457
      • Bronx Lebanon Hosp Ctr
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hosp
    • New York, New York, United States, 10032
      • Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10032
      • Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
    • New York, New York, United States, 10037
      • Harlem Hosp Ctr
  • North Carolina
    • Research Triangle Park, North Carolina, United States, 27709
      • Glaxo Wellcome Inc
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp / Baylor Univ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: McSherry G

Publications and helpful links

General Publications

• 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

Study record dates

Study Major Dates

• Study Completion (Actual): July 1, 1998

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Didanosine; Ribavirin
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Ribavirin; Didanosine
• Other Study ID Numbers: ACTG 274; 11250 (Registry Identifier: DAIDS ES Registry Number)