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

NCT ID: NCT00000833

Last Updated: 2021-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1998-07-31

Brief Summary

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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.

Detailed Description

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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. \[AS PER AMENDMENT 7/2/96: Note: In each cohort of 10 subjects at least 2 of 5 children from the older half of the cohort will have an ICD p24 antigen at entry.\]

Conditions

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HIV Infections

Keywords

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Ribavirin Didanosine Drug Therapy, Combination Acquired Immunodeficiency Syndrome AIDS-Related Complex Antiviral Agents

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Ribavirin

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

3 Months

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Van Dyke R

Role: STUDY_CHAIR

McSherry G

Role: STUDY_CHAIR

Locations

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Children's Hosp of Washington DC

Washington D.C., District of Columbia, United States

Site Status

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

Site Status

Schneider Children's Hosp

New Hyde Park, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

Harlem Hosp Ctr

New York, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Glaxo Wellcome Inc

Research Triangle Park, North Carolina, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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

Reference Type BACKGROUND

Other Identifiers

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11250

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 274

Identifier Type: -

Identifier Source: org_study_id