A Study of Azidothymidine in HIV-Infected Children
Status:
Completed
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)