CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
29 de julio de 2021 actualizado por: National Institute of Allergy and Infectious Diseases (NIAID)
Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients.
Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests).
A minimum of 176 subjects will be enrolled in the study.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (R-D+) liver transplant patients.Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir 900 mg orally once daily or preemptive therapy for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests.
Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality).
Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group.
Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment.
Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant.
A minimum of 176 subjects will be enrolled in the study.
Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176.
Subjects will be randomized into one of the two groups in 1:1 ratio.
The study duration is 7 years.
The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.
The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).
Tipo de estudio
Intervencionista
Inscripción (Actual)
205
Fase
- Fase 4
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90095-8358
- Ronald Reagan University of California Los Angeles Medical Center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322-1013
- Emory Clinic - Transplant Center
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905-0001
- Mayo Clinic, Rochester - Infectious Diseases
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New York
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New York, New York, Estados Unidos, 10029-6504
- Mount Sinai School of Medicine - Medicine - Infectious Diseases
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15213-3403
- University of Pittsburgh - Medicine - Infectious Diseases
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Washington
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Seattle, Washington, Estados Unidos, 98195-7110
- University of Washington - Medicine
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 99 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Be > / = 18 years of age.
- Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).
- Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.
- Have absolute neutrophil count > 1000/µL at randomization.
- If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.
-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.
- Subject or legally authorized representative has provided written informed consent.
Exclusion Criteria:
- Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.
- Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.
- Be breast-feeding mother.
- Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).
- Be undergoing multi organ transplant or have undergone prior organ transplant.
- Have expected life expectancy of less than 72 hours.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Preemptive Therapy
900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
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Comparador activo: Prophylaxis
900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation.
All dosages adjusted for renal dysfunction.
n=88
|
Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis.
Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of Cytomegalovirus (CMV) Disease.
Periodo de tiempo: 365 days post-transplant
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CMV disease as verified by an independent end point committee
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365 days post-transplant
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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All-cause Mortality
Periodo de tiempo: Up to 365 days post-transplant
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Survival probability at 1 year
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Up to 365 days post-transplant
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Incidence of Allograft Rejection
Periodo de tiempo: Up to 365 days post-transplant
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Number of subjects with allograft rejection
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Up to 365 days post-transplant
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Graft Loss
Periodo de tiempo: Up to 365 days post-transplant
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Incidence of graft loss (re-transplantation)
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Up to 365 days post-transplant
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Late-onset CMV Disease
Periodo de tiempo: Up to 365 days post-transplant
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Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee
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Up to 365 days post-transplant
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Bacterial Infections
Periodo de tiempo: Up to 365 days post-transplant
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Incidence of bacterial opportunistic infections
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Up to 365 days post-transplant
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Major Fungal Infections
Periodo de tiempo: Up to 365 days post-transplant
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Opportunistic fungal infections
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Up to 365 days post-transplant
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Major Non-CMV Viral Infections
Periodo de tiempo: Up to 365 days post-transplant
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Incidence of non-CMV viral infections
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Up to 365 days post-transplant
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Neutropenia
Periodo de tiempo: Day 1 through Day 107
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Incidence of neutropenia less than 1000/µL while on valganciclovir treatment
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Day 1 through Day 107
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Neutropenia Less Than 500
Periodo de tiempo: prior to day 107
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ANC less than 500 while on valganciclovir
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prior to day 107
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Hematopoietic Growth Factors
Periodo de tiempo: Day 1 through Day 107
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Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
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Day 1 through Day 107
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Risk Factors for Cytomegalovirus Viremia following Liver Transplantation With a Seropositive Donor and Seronegative Recipient Receiving Antiviral Therapy. J Infect Dis. 2021 Mar 29;223(6):1073-1077. doi: 10.1093/infdis/jiaa470.
- Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Stevens-Ayers T, Edmison B, Boeckh M, Limaye AP. Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial. JAMA. 2020 Apr 14;323(14):1378-1387. doi: 10.1001/jama.2020.3138.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
29 de octubre de 2012
Finalización primaria (Actual)
22 de junio de 2018
Finalización del estudio (Actual)
22 de junio de 2018
Fechas de registro del estudio
Enviado por primera vez
2 de marzo de 2012
Primero enviado que cumplió con los criterios de control de calidad
8 de marzo de 2012
Publicado por primera vez (Estimar)
13 de marzo de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
26 de agosto de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
29 de julio de 2021
Última verificación
22 de marzo de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 11-0073
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
No
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