Home
Search
Study Topics
Glossary
|
|
|
|
|
|
Sponsors and Collaborators: |
National Institute of Allergy and Infectious Diseases (NIAID) National Cancer Institute (NCI) |
---|---|
Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00000982 |
AMENDED 07/07/93: To evaluate whether continuous infusion AZT will impact neurodevelopmental deficits associated with HIV infection or alter rate of encephalopathy progression in children who have failed to improve or shown progression of these deficits despite optimal AZT therapy.
AMENDED: To assess whether didanosine (ddI) will be better tolerated than AZT administered by either continuous intravenous delivery or oral administration (ddI arm removed per amended version).To determine whether ddI will achieve comparable clinical efficacy as the continuous intravenous route of delivery of AZT, and to assess whether either or both of these regimens are superior to that achieved with an intermittent AZT dosage schedule. To determine whether there are differences in patient or parent (guardian) compliance between the three treatment regimens. Original design: To determine whether the pharmacokinetic profile (bloodstream levels) of zidovudine (AZT) influences its effectiveness on HIV infection in children. That is, the study seeks to find out whether there is a difference in the effect of AZT when given as a continuous intravenous infusion (and, if available, an oral sustained release dose) compared to an intermittent (not continuous) dose given orally every 6 hours. The study also plans to determine (1) whether there are differences in the tolerance and side effects associated with AZT when given on an intermittent schedule as opposed to a steady-state schedule; (2) the extent of variation from patient to patient in AZT levels and whether the plasma and cerebrospinal fluid levels of AZT are related to the degree of therapeutic effectiveness; and (3) whether there are differences in the response of children who acquired HIV infection perinatally (just before, during, or just after the time of birth) versus those who acquired HIV infection by transfusion.
One of the most serious effects of HIV disease in children is neuropsychological deterioration (relating to mental and nervous system functioning). This complication affects the vast majority of HIV infected children. A previous study of continuous intravenous administration of AZT in pediatric patients with HIV infection showed consistent and dramatic improvements of symptoms in all patients that had shown neurodevelopmental deficits or abnormalities. These improvements were seen within 3 to 4 weeks after AZT treatment was started. Neurodevelopmental improvements have been sustained on AZT, usually showing steady improvement which, in some patients, was associated with restoration of pre-HIV intellectual and neurological function. This study also showed an increase in the IQ scores of children receiving continuous infusion of AZT who did not have overt clinical evidence of encephalopathy (disease of the brain). Thus changes in cognitive function may be among the earliest signs of AIDS encephalopathy and underscores the need to start therapies that will treat the central nervous system in patients who appear to be clinically intact. A study comparing continuous infusion to intermittent dosing of AZT showed a significant increase in IQ scores for those children receiving the continuous dose compared to those treated with the intermittent schedule. Although a portable infusion pump allows patients to receive continuous infusion of AZT, a sustained release oral formulation that could provide a continuous release of AZT into the bloodstream would be highly desirable.
Condition | Intervention | Phase |
---|---|---|
Encephalopathy HIV Infections |
Drug: Zidovudine Drug: Didanosine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A Randomized Trial To Evaluate the Impact of Maintaining Steady-State Concentrations of Azidothymidine (AZT) Versus an Intermittent Schedule of AZT Delivery in Children With Symptomatic HIV Infection |
Estimated Enrollment: | 75 |
One of the most serious effects of HIV disease in children is neuropsychological deterioration (relating to mental and nervous system functioning). This complication affects the vast majority of HIV infected children. A previous study of continuous intravenous administration of AZT in pediatric patients with HIV infection showed consistent and dramatic improvements of symptoms in all patients that had shown neurodevelopmental deficits or abnormalities. These improvements were seen within 3 to 4 weeks after AZT treatment was started. Neurodevelopmental improvements have been sustained on AZT, usually showing steady improvement which, in some patients, was associated with restoration of pre-HIV intellectual and neurological function. This study also showed an increase in the IQ scores of children receiving continuous infusion of AZT who did not have overt clinical evidence of encephalopathy (disease of the brain). Thus changes in cognitive function may be among the earliest signs of AIDS encephalopathy and underscores the need to start therapies that will treat the central nervous system in patients who appear to be clinically intact. A study comparing continuous infusion to intermittent dosing of AZT showed a significant increase in IQ scores for those children receiving the continuous dose compared to those treated with the intermittent schedule. Although a portable infusion pump allows patients to receive continuous infusion of AZT, a sustained release oral formulation that could provide a continuous release of AZT into the bloodstream would be highly desirable.
AMENDED 07/07/93: Children with progressive encephalopathy who have received a minimum of 3 months of oral or intermittent AZT or who have failed to improve following 6 months of optimal AZT will receive continuous infusion AZT via a portable infusion pump.
AMENDED: The oral sustained release has been dropped and is now oral ddI. Added has been a planned stratification for randomization for patients who received any antiretroviral therapy 4 or more weeks prior to study entry. The informed consent was modified to reflect ddI toxicities from adult studies. Computerized Tomography radiation dosimetry is now included.
AMENDED: Dropping the ddI component and open only to children with encephalopathy meaning they are losing milestones, this is equal to a P2 CDC rating . Testing the difference in intermediate vs continuous AZT. 12/1990. Original design: Children are first evaluated for randomization according to whether they have or do not have evidence of neurodevelopmental deficits at the time of the initial pretreatment evaluation. Patients are assigned to 1 of 3 groups, to receive AZT (1) by continuous infusion; (2) by oral, intermittent (every 6 hours) dosing; or (3) by oral sustained-release dosing. If the oral sustained-release formulation is not available when this study begins, it will begin with only the first 2 groups. The sustained release preparation will be evaluated as soon as it is available. Patients will be tested to measure physical or biological improvement in neurodevelopmental function.
Ages Eligible for Study: | 3 Months to 12 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
AMENDED 07/07/93:
Only HIV-related encephalopathy patients eligible (i.e., children with progressive encephalopathy who have received a minimum of 3 months of oral or intermittent AZT or who have failed to improve following 6 months of optimal AZT).
ORIGINAL DESIGN:
Eligibility criteria used are similar to those being used in the "Multicenter Trial to Evaluate Oral Retrovir in the Treatment of Children with Symptomatic HIV Infection," currently Protocol 88 C-92a.
Children are included:
Prior Medication:
Allowed within 4 weeks of study entry:
Exclusion Criteria
Co-existing Condition:
Patients with the following are excluded:
Concurrent Medication:
Excluded:
Patients with the following are excluded:
Prior Medication:
Excluded within 4 weeks of study entry:
Prior Treatment:
Excluded within 4 weeks of study entry:
Risk Behavior:
Excluded:
United States, District of Columbia | |
Children's Hosp of Washington DC / Children's Natl Med Ctr | |
Washington, District of Columbia, United States, 20010 | |
United States, Florida | |
Univ of Florida Med Ctr | |
Jacksonville, Florida, United States, 32209 | |
United States, Maryland | |
Univ of Maryland at Baltimore / Univ Med Ctr | |
Baltimore, Maryland, United States, 21201 | |
Natl Cancer Institute / HIV / AIDS Malignancy Branch | |
Bethesda, Maryland, United States, 20892 | |
Walter Reed / USUHS / Pediatrics | |
Bethesda, Maryland, United States, 208894799 | |
United States, New York | |
Children's Hosp at Albany Med Ctr | |
Albany, New York, United States, 12208 | |
United States, North Carolina | |
Duke Univ Med Ctr | |
Durham, North Carolina, United States, 277103499 |
Study Chair: | Pizzo PA |
Study ID Numbers: | ACTG 103, NCI 89 C-102C |
Study First Received: | November 2, 1999 |
Last Updated: | August 7, 2008 |
ClinicalTrials.gov Identifier: | NCT00000982 |
Health Authority: | United States: Federal Government |
Central Nervous System Diseases Acquired Immunodeficiency Syndrome Zidovudine |
Virus Diseases Sexually Transmitted Diseases, Viral Didanosine HIV Infections Sexually Transmitted Diseases |
Acquired Immunodeficiency Syndrome Zidovudine Central Nervous System Diseases Retroviridae Infections Immunologic Deficiency Syndromes |
Antimetabolites Anti-Infective Agents Communicable Diseases RNA Virus Infections Anti-HIV Agents Slow Virus Diseases Immune System Diseases Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |
Infection Antiviral Agents Pharmacologic Actions Reverse Transcriptase Inhibitors Anti-Retroviral Agents Therapeutic Uses Lentivirus Infections Nucleic Acid Synthesis Inhibitors |