Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000982
Status:
COMPLETED
Last Update Posted:
2011-03-14
First Post:
1999-11-02
Brief Title:
A Study of Azidothymidine in HIV-Infected Children
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
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
Status:
COMPLETED
Status Verified Date:
1996-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
AMENDED 070793 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 versionTo 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
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 versionTo 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
Detailed Description:
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 070793 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 121990 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
AMENDED 070793 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 121990 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
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI 89 C-102C | None | None | None |