Profilaxis con rezafungina en trasplante de hígado
Profilaxis con rezafungina en trasplantes de hígado con alto riesgo de infección fúngica invasiva
This is an interventional study to evaluate the efficacy of rezafungin, a new echinocandin, for the prevention of invasive fungal infections (IFIs) after liver transplantation. Patients who receive rezafungin will be compared to a similar group of patients who underwent liver transplantation in the preceding two years for the incidence of IFIs.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a single arm interventional study of consecutive liver transplant recipients who have consented to this rezafungin prophylaxis study. The outcome will be compared with that of similar group of patients not enrolled in the study and those who underwent liver transplant in the preceding two years (historical controls). Propensity score matching will be used to select retrospective cohort.
There will be 3 groups:
- Study group (prospective intervention cohort): Rezafungin (180 patients)
- Prospective control group (prospective control cohort): Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's tiered antifungal prophylaxis standard of care (20 patients: 10 who receive fluconazole/voriconazole and 10 who do not receive fluconazole/voriconazole)
- Historical control group (retrospective control cohort): Patients at risk for IFI who received fluconazole/voriconazole (tier approach) in the two years preceding this study (180 patients)
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Estados Unidos, 15213
- UPMC Presbyterian
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Liver transplant recipient
- 18 years of age or older
- ≥1 risk factor(s) for IFI: living donor transplant, retransplantation, complicated operations (based on duration of transplant and number of blood products required in the peri-transplant period), choledochojejunostomy anastomosis, or peri-operative Candida colonization, recent Candida infection, renal replacement therapy post-transplant, and reoperation within the first 90 days of transplant.
Exclusion Criteria:
- Participants who are perceived not to survive past 7 days after transplant
- Participants who elect not to participate in the prospective trial
- Participants who had active candidiasis at the time of transplant
- Participants with a history of allergy to an echinocandin
- Participants who are pregnant.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Prospective Intervention Cohort
Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV once weekly for a total duration of 4 weeks |
Rezafungin 400 mg IV once within 24 hours of liver transplant, followed by 200 mg IV weekly for 4 weeks. |
|
Comparador activo: Prospective Control Cohort
Patients who receive fluconazole/voriconazole or no antifungal prophylaxis as part of UPMC's risk-based antifungal prophylaxis standard of care after liver transplant |
UPMC uses a tiered approach to antifungal prophylaxis, based on risk factors for IFI. Fluconazole is used for recipients with risk factors for yeast infections: choledochojejunostomy, prolonged transplant time, receipt of >40 units of blood products within 24 hours of transplant, and Candida colonization or infection within 3 months prior to transplant. Voriconazole is used for recipients with risk factors for mould infections: re-transplantation, renal failure requiring renal replacement therapy, fulminant hepatic failure as indication for transplant, intra-abdominal/thoracic re-exploration within the first month after transplant. No prophylaxis is given if there are no risk factors for yeast or mould infections.
Otros nombres:
|
|
Comparador activo: Historical Control Group
Patients at risk for IFI who received fluconazole/voriconazole for antifungal prophylaxis after liver transplant in the two years preceding the study |
UPMC uses a tiered approach to antifungal prophylaxis, based on risk factors for IFI. Fluconazole is used for recipients with risk factors for yeast infections: choledochojejunostomy, prolonged transplant time, receipt of >40 units of blood products within 24 hours of transplant, and Candida colonization or infection within 3 months prior to transplant. Voriconazole is used for recipients with risk factors for mould infections: re-transplantation, renal failure requiring renal replacement therapy, fulminant hepatic failure as indication for transplant, intra-abdominal/thoracic re-exploration within the first month after transplant. No prophylaxis is given if there are no risk factors for yeast or mould infections.
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence of proven and probable IFIs
Periodo de tiempo: 90 days post-transplant
|
Incidence of proven and probable IFIs within 90 days post-transplant |
90 days post-transplant
|
|
Incidence of proven and probable breakthrough IFI
Periodo de tiempo: While receiving rezafungin, voriconazole, or fluconazole
|
Incidence of breakthrough IFI while on specific antifungal prophylaxis |
While receiving rezafungin, voriconazole, or fluconazole
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Fungal-free survival
Periodo de tiempo: 90 days and 6 months post-transplant
|
Number of participants without fungal infection |
90 days and 6 months post-transplant
|
|
Fungal colonization
Periodo de tiempo: 90 days and 6 months post-transplant
|
Number of participants with presence or growth of fungi without it causing active infection or disease |
90 days and 6 months post-transplant
|
|
Graft rejection
Periodo de tiempo: 90 days and 6 months post-transplant
|
Number of participants with liver allograft acute rejection |
90 days and 6 months post-transplant
|
|
Graft loss
Periodo de tiempo: 90 days 6 months post-transplant
|
Number of participants with failure of the liver allograft to function adequately or to remain viable |
90 days 6 months post-transplant
|
|
All-cause mortality
Periodo de tiempo: 90 days 6 months post-transplant
|
Number of participants who die |
90 days 6 months post-transplant
|
|
Number of participants with premature discontinuation of prophylaxis
Periodo de tiempo: 90 days post-transplant
|
Number of patients who experience an adverse event requiring premature discontinuation of antifungal prophylaxis |
90 days post-transplant
|
|
Overall incidence of development of antifungal resistance
Periodo de tiempo: Within 6 months of transplant
|
Antifungal resistance of breakthrough fungal organisms or fungal organisms recovered within the first 6 months of transplant for patients who received rezafungin |
Within 6 months of transplant
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Pharmakokinectics (PK) of rezafungin
Periodo de tiempo: Up to 4 weeks post-transplant
|
Pharmacokinetics of rezafungin while in ICU to assess the PK during the peri-transplant period |
Up to 4 weeks post-transplant
|
|
Stool microbiota composition
Periodo de tiempo: Within 6 months post-transplant
|
Stool microbiota and fecal Candida constituent and susceptibility profile in response to rezafungin |
Within 6 months post-transplant
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Fernanda Silveira, University of Pittsburgh
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
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
Otros números de identificación del estudio
- STUDY24080165
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
We do not plan to share individual participant data outside of our investigative team and collaborators. Aggregate data will be shared in publications as appropriate.
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. .