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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 300
- Locations
- 52
Study Overview
Brief Summary
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.
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.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 3 Months to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Concurrent Medication:
- •Prophylaxis treatment for Pneumocystis carinii pneumonia (PCP).
- •Immunoglobulin.
- •Maintenance therapy with amphotericin B (l mg/kg) up to 5 days/week.
- •Concurrent Treatment:
- •Blood transfusions.
- •Prior Medication:
- •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
- •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:
- •Zidovudine (AZT), other antiretroviral agents, biological modifiers, and investigational medications.
- •Drugs with potential to cause peripheral neuropathy or pancreatitis.
- •Patients with the following are excluded:
- •Active malignancy requiring concomitant chemotherapy.
- •Prior Medication:
- •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.