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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

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Qué se está evaluando

Colección de datos

Quiénes están siendo reclutados

Enfermedades Transmisibles+15

+ Enfermedades Urogenitales

+ Enfermedades del Sistema Nervioso Central

De 3 meses a 12 años
Ver todos los criterios de elegibilidad
Cómo está diseñado el estudio

Estudio de Tratamiento

Fase 2
Intervencional
Ver detalles del protocolo

Resumen

Patrocinador PrincipalNational Institute of Allergy and Infectious Diseases (NIAID)
Última actualización: 27 de enero de 2026
Extraido de una base de datos validada por el gobierno.Reclamar como socio

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.

Título OficialA 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
NCT00000982
Patrocinador PrincipalNational Institute of Allergy and Infectious Diseases (NIAID)
Última actualización: 27 de enero de 2026
Extraido de una base de datos validada por el gobierno.Reclamar como socio

Protocolo

Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.
Detalles del Diseño

Se reclutarán 75 pacientes

Número total de participantes que el ensayo clínico espera reclutar.

Estudio de Tratamiento

Estos estudios prueban nuevas formas de tratar una enfermedad, condición o problema de salud. El objetivo es determinar si un nuevo medicamento, terapia o enfoque funciona mejor o tiene menos efectos secundarios que las opciones existentes.

Elegibilidad

Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.
Condiciones
Criterios

Cualquier sexo

Sexo biológico de los participantes elegibles para inscribirse.

De 3 meses a 12 años

Rango de edades de los participantes que pueden unirse al estudio.

Voluntarios sanos no permitidos

Indica si personas sanas, sin la condición que se estudia, pueden participar.

Condiciones

Patología

Enfermedades TransmisiblesEnfermedades UrogenitalesEnfermedades del Sistema Nervioso CentralSíndrome de Inmunodeficiencia AdquiridaInfecciones Transmitidas por la SangreEnfermedades del CerebroEnfermedades GenitalesEnfermedades del sistema inmunitarioSíndromes de Deficiencia InmunológicaInfeccionesEnfermedades del sistema nerviosoInfecciones por RetroviridaeInfecciones por virus de ARNEnfermedades de Transmisión SexualEnfermedades por virus lentoEnfermedades ViralesEnfermedades de transmisión sexual, viralesInfecciones por VIH

Criterios

Inclusion Criteria Concurrent Medication: Allowed: * Steroids for children with lymphocytic interstitial pneumonitis (LIP) who are steroid dependent. * Maintenance amphotericin B and antituberculosis chemotherapy. * Immunoglobulin therapy for children who develop at least three serious bacterial infections while receiving zidovudine (AZT) therapy. * Prophylactic therapy for children who have had a previous episode of Pneumocystis carinii pneumonia (PCP) and who are receiving such therapy. 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: * With overt encephalopathy as well as those who may have a subclinical cognitive impairment. * Children must have laboratory evidence of HIV infection as demonstrated by either a positive viral culture (blood or cerebrospinal fluid) or detectable serum P24 antigen or repeatedly positive test for HIV antibody. HIV antibody must be determined by federally licensed ELISA test and confirmed by Western blot. * Children with AIDS or ARC must have at least one of the following laboratory criteria indicative of immunologic abnormality: * Hypergammaglobulinemia (IgG or IgA) defined as immunoglobulin values greater than upper limit of the age-adjusted normal. * Hypogammaglobulinemia (IgG or IgA) defined as immunoglobulin levels less than lower limit of the age-adjusted normal. * Absolute depression in CD4+ cells of 500 cells/mm3 or less. * Decreased helper/suppressor ratio of 1.0 or less. * Depressed in vitro mitogen response to at least one antigen (pokeweed, phytohemagglutinin, concanavalin A, Staphylococcus aureus, tetanus toxoid, Candida). * Parent or guardian available to give written informed consent. Prior Medication: Allowed within 4 weeks of study entry: * Immunoglobulin for thrombocytopenia. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: * Serious bacterial, fungal, or parasitic infections requiring parenteral therapy, at the time of study entry. Concurrent Medication: Excluded: * Clofazimine, ansamycin (or other experimental agents or agents that may modify zidovudine (AZT) toxicity or safety) for active chronic opportunistic infection at time of study entry. * Chronic use of drugs that are metabolized by hepatic glucuronidation (and may alter the metabolism of AZT) (e.g., acetaminophen). * Prophylaxis for Pneumocystis carinii pneumonia (PCP) for children who have not had a previous episode of PCP, oral candidiasis, or otitis media. * Immunoglobulin therapy not specifically allowed. Patients with the following are excluded: * Serious bacterial, fungal, or parasitic infections requiring parenteral therapy, at the time of study entry. * Lymphocytic interstitial pneumonitis (LIP) and no additional AIDS-defining indicator disease as specified in the CDC Surveillance Case Definition for AIDS. Prior Medication: Excluded within 4 weeks of study entry: * Other antiretroviral agents including ribavirin, HPA-23, dideoxycytosine (ddC), soluble CD4, and dideoxyadenosine (ddA) / didanosine (ddI). * Immunomodulating agents including steroids, interferon, isoprinosine, and IL-2 not specifically allowed. * Immunoglobulin not specifically allowed. * Excluded within 2 weeks of study entry: * Any other experimental therapy. * Drugs that cause prolonged neutropenia or significant nephrotoxicity. Prior Treatment: Excluded within 4 weeks of study entry: * Lymphocyte transfusion for immune reconstitution. * Excluded within 3 months of study entry: * Bone marrow transplant. Risk Behavior: Excluded: * Active alcohol or drug abuse.

Centros del Estudio

Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.

Este estudio tiene 7 ubicaciones

Suspendido

Children's Hosp of Washington DC / Children's Natl Med Ctr

Washington D.C., United StatesAbrir Children's Hosp of Washington DC / Children's Natl Med Ctr en Google Maps
Suspendido

Univ of Florida Med Ctr

Jacksonville, United States
Suspendido

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, United States
Suspendido

Walter Reed / USUHS / Pediatrics

Bethesda, United States
Completado7 Centros de Estudio