A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

Study Overview
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Brief Summary
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To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Detailed Description
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AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children. Patients are placed by random selection into one of three groups to receive either AZT alone, ddI alone, or AZT and ddI. This is a double-blind study: neither patient nor treating physician knows which group patient is in. If patients are receiving either AZT or ddI alone and they develop drug toxicity (after dose reduction), or if HIV disease progresses, the alternative single drug is offered. If patients receiving both drugs develop drug toxicity (despite dose reduction) or if HIV disease progresses, they discontinue study drug and are offered the best alternative therapy. PER AMENDMENT 6/26/95: Initial monotherapy AZT arm is unblinded and no further crossover therapy for any arm is permitted. Patients who reach crossover criteria on initial blinded ddI or AZT+ddI will be unblinded and permanently discontinued from study drugs.

Official Title
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A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Zidovudine
* Drug: Didanosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Concurrent Medication: Allowed: Acetaminophen, ibuprofen, or aspirin, but not on a continual basis for > 72 hours. Systemic ketoconazole and fluconazole for acute therapy. Recommended: Prophylaxis for PCP. (Primary prophylaxis with TMP / SMX is encouraged.) IV pentamidine may be used in selected cases if not administered on a weekly basis. Patients must have the following: HIV infection. Children randomized prior to their eighteenth birthday are eligible. Co-enrollment in either ACTG 179 or 189 is permitted. Prior Medication: Allowed: Up to six weeks of antiretroviral or immunomodulator treatment excluding steroids and intravenous immunoglobulin. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Active malignancy. Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms. History of uncontrolled seizure disorder. Grade 3 or higher peripheral neuropathy. Cardiomyopathy. Concurrent Medication: Excluded: Chemotherapy for malignancy. Oral acidifying agents. Acetaminophen, ibuprofen, or aspirin on a continual basis for > 72 hours. Ketoconazole or fluconazole for prophylaxis. Drugs with potential to cause peripheral neuropathy or pancreatitis should not be given daily for > 4 weeks. Patients with the following are excluded: Active malignancy. Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms. History of uncontrolled seizure disorder. Grade 3 or higher peripheral neuropathy. Prior Medication: Excluded: Steroids. Intravenous immunoglobulin. Antiretroviral drugs or specific immunomodulator treatment (excluding steroids and intravenous immunoglobulin) for > 6 weeks and within 7 days prior to study entry. Prior Treatment: Excluded: Red blood cell transfusion within four weeks prior to study entry. Ongoing drug or alcohol use.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Zidovudine|nan|
|Drug: Didanosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Didanosine, Drug Evaluation, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine