Letermovir vs Valganciclovir in CMV R+ Kidney Transplant
Letermovir Versus Valganciclovir for 90 Days in CMV Seropositive Kidney Transplant Recipients: Results of a Single-center Experience.
The purpose of this study is to find out whether letermovir can help prevent cytomegalovirus (CMV) infection in kidney transplant recipients who are CMV seropositive. To do this, researchers will compare patients who received letermovir with a group of historical patients who received valganciclovir ("mini dose"). Both groups will be on CMV prophylaxis drug for 90 days post-transplant.
The main question the study wants to answer is:
• Does letermovir work as well as valganciclovir in preventing CMV infections during the first 12 months after a kidney transplant?
The study will also look at other important questions:
- Is letermovir easier for patients to tolerate than valganciclovir?
- How long does it take for a CMV infection to appear in each group?
- Are there differences in "breakthrough" CMV infections between the two medications?
- For patients who develop CMV that becomes resistant to treatment, are the resistance patterns different between the two groups
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The purpose of this study is to evaluate the efficacy and tolerability of letermovir compared to standard-of-care, valganciclovir, for the prevention of clinically significant cytomegalovirus (CMV) infection in CMV moderate risk adult kidney transplant recipients.
A 3:1 match of historical valganciclvoir:letermovir arm
• Matching criteria:
- Induction agent: lymphocyte-depleting (rabbit anti-thymocyte globulin or alemtuzumab) versus non-lymphocyte depleting (basiliximab)
- Delayed graft function (dialysis within one week of kidney transplant)
- MMF dose at de novo discharge (weight-based vs non-weight based)
Study Arms:
Letermovir Arm:
- Letermovir 480 mg PO daily starting POD 4 through 10 OR
- Letermovir 240 mg PO daily if given concomitantly with cyclosporine, for 90 days
- Will be given with acyclovir 400 mg PO BID (or 200 PO BID if CrCl <25) for 90 days
Historical Arm:
Valganciclovir 450 mg PO daily (adjusted for renal function) for 90 days
- CrCl 25-30: valganciclovir 450 mg PO q 48 h
- CrCl <25: Valganciclovir 450 mg PO three times weekly
Outcomes:
Primary Efficacy Objective:
Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir
- Clinically Significant CMV Infection: CMV disease or symptomatic viremia requiring therapeutic intervention
Secondary Objectives:
Tolerability:
- Proportion of patients with leukopenia or neutropenia (composite) in patients who received letermovir versus standard of care valganciclovir
- Leukopenia: white blood cells < 3500 cells/uL
Neutropenia: absolute neutrophil count < 1000 cells/uL
- Intolerability or early drug discontinuation
Proportion of patients who discontinue the study drug prematurely due to adverse events or intolerance
o Efficacy:
- Time-to clinically significant CMV infection (days)
- Breakthrough CMV while on CMV prophylaxis
CMV Viremia
- Detection of CMV DNA in blood via PCR
Clinically significant CMV infection
- CMV resistance
- Detection of CMV strains with genotypic or phenotypic resistance to antiviral agents used in prophylaxis or treatment
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Elisabeth Kincaide, PharmD
- Número de teléfono: 210-743-4086
- Correo electrónico: Elisabeth.Kincaide@uhtx.com
Copia de seguridad de contactos de estudio
- Nombre: Sean Moore, BSN, RN
- Número de teléfono: 210-475-2559
- Correo electrónico: Sean.Moore2@uhtx.com
Ubicaciones de estudio
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-
Texas
-
San Antonio, Texas, Estados Unidos, 78229
- University Hospital
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Contacto:
- Elisabeth Kincaide, PharmD
- Número de teléfono: 210-743-4086
- Correo electrónico: Elisabeth.Kincaide@uhtx.com
-
Contacto:
- Sean Moore, BSN, RN
- Número de teléfono: 210-475-2559
- Correo electrónico: Sean.Moore2@uhtx.com
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria (both arms):
- ≥18 years old
- Kidney transplant recipient with documented CMV IgG seropositive status (R+) within 90 days prior to transplant
Inclusion Criteria (letermovir arm):
- Males agree to use contraception and refraining from donating sperm for 290 days post-treatment initiation
- Females of child-bearing potential agree to follow contraception guidance for 290 days post-treatment initiation
Exclusion Criteria (both arms):
- Multiorgan organ transplant
- Received previous solid organ transplant or HSCT
- Unable to take oral medications
- Uncontrolled infections at the time of enrollment
- Hemodynamically unstable or on mechanical ventilation at the time of enrollment
- Documented HBsAg or detectable HCV RNA 90 days prior to enrollment or HCV+ donor
- Pregnant or breastfeeding or planning to be pregnant, breastfeeding or donating eggs during study period and 90 days post cessation
- Received any anti-CMV drug treatment within 7 days prior to enrollment
- Current user of recreational or illicit drugs or alcohol dependence
- History of CMV disease prior to enrollment
Exclusion Criteria (letermovir arm):
- Previously participated in a letermovir study or any other study with CMV investigational agents
- On dialysis or plasmapheresis at the time of enrollment
- Known or suspected hypersensitivity to active or inactive ingredients from letermovir or acyclovir formulations
- Child-Pugh Class C severe hepatic insufficiency
- Currently participating or has participated in a study with an unapproved compound of device within 28 days or 5 half-lives of this study
- Contraindications per letermovir or acyclovir package insert: patients on pimozide, ergot alkaloids; or pitavastatin and simvastatin when co-administered with cyclosporine
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 |
|---|---|
|
Comparador activo: Letermovir
Prospective letermovir prophylaxis
|
Letermovir 480 mg PO daily or 240 mg PO daily (if on cyclosporine) for 90 days post kidney transplant
|
|
Otro: Valganciclovir
Historical valganciclovir prophylaxis
|
Valganciclovir 450 mg PO daily for 90 days post kidney transplant (Historical Control)
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
CMV Infection
Periodo de tiempo: 12 months post kidney transplant
|
Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir.
|
12 months post kidney transplant
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
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
- STUDY00000831
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (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.
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