- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT05413811
Aceptabilidad y viabilidad del tratamiento combinado para el precáncer de cuello uterino entre mujeres sudafricanas que viven con el VIH (ACT 2)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Actualmente no se recomiendan terapias médicas para promover la eliminación de la infección por el virus del papiloma humano (VPH), la regresión de la displasia cervical o el tratamiento de la neoplasia intraepitelial cervical (CIN). Las mujeres infectadas con el virus de la inmunodeficiencia humana (VIH) tienen un mayor riesgo de infección por VPH, con tasas que alcanzan el 45 % - 90 %. A pesar de ser prevenibles, las anomalías citológicas, el precáncer de cuello uterino (neoplasia intraepitelial cervical de alto grado [CIN2/3]) y el cáncer de cuello uterino invasivo también ocurren con mayor frecuencia en mujeres infectadas por el VIH.
Este estudio está evaluando si el 5-fluorouracilo (5FU) tópico se puede usar como un tratamiento adyuvante controlado por el paciente para el precáncer de cuello uterino (CIN2/3) para ser autoadministrado después de la escisión quirúrgica para reducir el riesgo de CIN2/3 persistente/recurrente y progresión al cáncer de cuello uterino entre las mujeres infectadas por el VIH.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Johannesburg
-
Westdene, Johannesburg, Sudáfrica, 2092
- Clinical HIV Research Unit Temba Lethu Wing Helen Joseph Hospital
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Descripción
Criterios de inclusión:
- Infección por VIH-1 confirmada
- En terapia antirretroviral (ART), durante al menos 90 días antes de la inscripción
- Biopsia cervical que demuestra CIN2/3 dentro de los 120 días anteriores.
Criterio de exclusión:
- el embarazo,
- amamantamiento,
- tiene la intención de quedar embarazada dentro de los 180 días posteriores a la inscripción
- tiene una infección de transmisión sexual activa (las mujeres pueden participar una vez tratadas)
- tener un cuello uterino quirúrgicamente ausente
- tiene antecedentes de cáncer anogenital (cervical, vaginal, vulvar o anal) o una biopsia sospechosa de cáncer de cuello uterino
- tener una comorbilidad médica que podría interferir con la participación en el estudio.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 5 Fluorouracil (5FU) Cream
Participants self-administered 2 grams intravaginal 5FU cream at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
|
Quimioterapia tópica intravaginal, crema de 5-fluorouracilo
Otros nombres:
|
|
Comparador de placebos: Placebo Cream
Participants self-administered intravaginal placebo cream (an inert emollient that mimics the 5FU cream) at study weeks 4, 6, 8, 10, 12, 14, 16, and 18 (8 doses over 16 weeks total).
|
Crema placebo tópica intravaginal
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants Retained in the Study Through Week 24
Periodo de tiempo: Baseline (Week 0) through Week 24
|
Retention was defined as the number of participants who remained in follow-up and completed the Week 24 study visit.
The number and percentage of participants retained at Week 24 were reported for each study arm.
|
Baseline (Week 0) through Week 24
|
|
Number of Participants With ≥80% Acceptability Summary Score at Week 10
Periodo de tiempo: Week 10
|
Acceptability was defined as a summary score ≥80% on a 7-item questionnaire administered at Week 10.
Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28.
A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score.
The number and percentage of participants meeting this definition were reported for each study arm.
|
Week 10
|
|
Number of Participants With ≥80% Acceptability Summary Score by Week 24
Periodo de tiempo: Week 24
|
Acceptability was defined as a summary score ≥80% on the same 7-item questionnaire administered at Week 24.
Each item was rated on a 5-point Likert scale and coded from 0 (lowest acceptability) to 4 (highest acceptability), yielding a total possible score of 0 to 28.
A summary acceptability score was calculated as a percentage (0% to 100%) of the total possible score.
The number and percentage of participants meeting this definition were reported for each study arm.
|
Week 24
|
|
Number of Participants Experiencing a Treatment-Related Grade ≥2 Adverse Event or Grade 1 Genital Lesion
Periodo de tiempo: Week 4 (randomization) through Week 24
|
A safety event was defined as any Grade 2 or higher adverse event (AE), or any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to the study drug.
Adverse events were assessed from Week 4 (randomization) through Week 24.
The number and percentage of participants experiencing at least one such event were reported for each study arm.
|
Week 4 (randomization) through Week 24
|
|
Number of Participants Unable or Unwilling to Apply ≥50% of Study Cream Doses Due to Dose-Limiting Toxicity
Periodo de tiempo: Week 4 (randomization) through Week 18
|
A tolerability event was defined as inability or unwillingness to apply ≥4 of 8 planned doses of the study treatment due to a dose-limiting toxicity (DLT).
A DLT was defined as (1) any Grade 2 or higher AE, or (2) any Grade 1 AE involving a genital lesion (blister, ulceration, or pustule), that was assessed as possibly, probably, or definitely related to study drug and resulted in an investigator decision to reduce the number of doses or discontinue study treatment.
Tolerability was assessed from randomization through the dosing period (Week 18), with follow-up censored at the last tolerability assessment for participants who exited early without experiencing an event.
The number and percentage of participants experiencing a tolerability event were reported for each study arm.
|
Week 4 (randomization) through Week 18
|
|
Number of Participants Adherent to ≥75% of Study Cream Doses Based on Ultraviolet Inspection
Periodo de tiempo: Week 4 (randomization) through Week 24
|
Adherence was defined as administration of at ≥6 of 8 planned doses of study treatment, as determined by ultraviolet inspection of returned applicators.
Applicator collection occurred through Week 24, including for participants who completed dosing earlier, to allow complete ascertainment of dose use.
Each applicator was independently assessed by ≥2 reviewers; in cases of disagreement, a third reviewer adjudicated the result.
Participants were classified as adherent if ≥6 applicators showed evidence of use.
Participants who did not meet this threshold, including those with missing or incomplete applicator data, were classified as non-adherent.
The number and percentage of participants meeting this definition were reported for each study arm.
|
Week 4 (randomization) through Week 24
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Percent of Participants With CIN2/3 at Baseline Who Regressed to CIN1 or Normal Histology at Week 24
Periodo de tiempo: Baseline (Week 0) through Week 24
|
The analysis population included all randomized participants, all of whom had CIN2 or CIN3 at baseline (Week 0) confirmed by loop electrosurgical excision procedure (LEEP) histology.
The analysis population was restricted to participants who completed the Week 24 visit and had cervical biopsy results available.
This included 89 participants in the placebo arm and 81 participants in the 5FU arm.
Regression was defined as improvement from CIN2 or CIN3 at baseline to CIN1 or normal histology at Week 24, as assessed by cervical biopsy.
Participants missing Week 24 data were not included and not considered to have experienced CIN2/3 regression.
The number and percentage of participants meeting this definition were reported for each study arm.
The Wilson score method was used to estimate 95% confidence intervals around percentages.
|
Baseline (Week 0) through Week 24
|
|
Percent of Participants With Baseline High-Risk HPV Who Achieved Genotype-Specific Clearance at Week 24
Periodo de tiempo: Baseline (Week 0) through Week 24
|
The analysis population was restricted to participants with at least one high-risk HPV (hrHPV) genotype detected at baseline and with hrHPV results available at Week 24.
A total of 69 participants in the 5FU arm and 80 participants in the placebo arm met these criteria.
High-risk HPV clearance was defined as absence at Week 24 of all hrHPV genotypes detected at baseline.
Participants without baseline hrHPV infection or without Week 24 hrHPV results were excluded from this analysis.
The number and percentage of participants meeting this definition were reported for each study arm.
The Wilson score method was used to estimate 95% confidence intervals around percentages.
|
Baseline (Week 0) through Week 24
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Carla Chibwesha, MD, MSc, University of North Carolina, Chapel Hill
Publicaciones y enlaces útiles
Publicaciones Generales
- Chibwesha CJ, Mollan KR, Teodoro NS, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. ACT 2 Clinical Trial Design: Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living with HIV. medRxiv [Preprint]. 2025 Aug 14:2025.08.12.25333540. doi: 10.1101/2025.08.12.25333540.
- Teodoro NS, Mollan KR, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Mischell MA, Rahangdale L, Chibwesha CJ. Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among Women Living with HIV in South Africa: Primary Outcomes from the ACT 2 Randomized Trial. medRxiv [Preprint]. 2026 Mar 16:2026.03.14.26348308. doi: 10.64898/2026.03.14.26348308.
- Chibwesha CJ, Teodoro NS, Mollan KR, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. Efficacy of Combination Treatment for Cervical Precancer Among Women Living with HIV in South Africa: Secondary Outcomes from the ACT 2 Randomized Controlled Trial. medRxiv [Preprint]. 2026 Mar 22:2026.03.19.26348810. doi: 10.64898/2026.03.19.26348810.
- Chibwesha CJ, Mollan KR, Teodoro NS, Keys JR, Liu C, Mulongo M, Gumede S, Pasipamire T, Faesen M, Rahangdale L. Randomized clinical trial protocol: Acceptability and feasibility of combination treatment for cervical precancer among South African women living with HIV (ACT 2). Contemp Clin Trials. 2026 May;164:108272. doi: 10.1016/j.cct.2026.108272. Epub 2026 Mar 2.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones transmitidas por la sangre
- Enfermedades urogenitales
- Enfermedades Genitales
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedades del sistema inmunológico
- Infecciones
- Infecciones por virus de ARN
- Enfermedades virales
- Enfermedades uterinas
- Enfermedades Genitales Femeninas
- Enfermedades contagiosas
- Enfermedades De Transmisión Sexual Virales
- Enfermedades de transmisión sexual
- Infecciones por lentivirus
- Infecciones por retroviridae
- Síndromes de deficiencia inmunológica
- Neoplasias Genitales Femeninas
- Enfermedades de virus lentos
- Enfermedades del cuello uterino
- Neoplasias Uterinas
- Infecciones por VIH
- Síndrome de inmunodeficiencia adquirida
- Neoplasias del cuello uterino
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Pirimidinas
- Uracílico
- Pirimidinonas
- Fluorouracilo
Otros números de identificación del estudio
- IGHID12046
- 1R01CA250850-01 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .