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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000833
First received: November 2, 1999
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
HIV Infections
Drug: Ribavirin
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Phase I Study of Combination Therapy With Didanosine (ddI) and Ribavirin in HIV-Infected Children.

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 20
Study Completion Date: July 1998
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.]

  Eligibility

Ages Eligible for Study:   3 Months to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000833

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

Additional Information:
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000833     History of Changes
Other Study ID Numbers: ACTG 274, 11250
Study First Received: November 2, 1999
Last Updated: May 1, 2012
Health Authority: United States: Federal Government

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
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 28, 2014