A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Zidovudine Drug: Didanosine |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Masking: Double-Blind Primary Purpose: Treatment |
| Official Title: | A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children |
| Estimated Enrollment: | 819 |
| Study Completion Date: | September 1996 |
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.
Eligibility| Ages Eligible for Study: | 3 Months to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Show 80 Study Locations| Study Chair: | Baker C | |
| Study Chair: | Englund J |
More Information
Additional Information:
Publications:
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000637 History of Changes |
| Other Study ID Numbers: | ACTG 152, 11127 |
| Study First Received: | November 2, 1999 |
| Last Updated: | March 29, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
Didanosine Drug Evaluation Drug Therapy, Combination |
Acquired Immunodeficiency Syndrome AIDS-Related Complex Zidovudine |
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 |
Zidovudine 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 June 13, 2013