Extended Validation of Donor-derived Cell-free DNA in Kidney Transplant Recipients (VALiDATE)
3 de septiembre de 2026 actualizado por: Paris Translational Research Center for Organ Transplantation
Multinational Study to Evaluate the Performance of Donor-derived Cell-free DNA in Detecting Kidney Allograft Rejection Across Context of Use, Populations, and Injury Phenotypes
This is a multinational, multi-center, observational cohort study.
Kidney allograft rejection is poorly detected by standard-of-care biomarkers. Although dd-cfDNA has been associated with improved rejection detection when added to standard-of-care biomarkers and clinical parameters, little is known about its performance across Banff 2022 rejection phenotypes and injury patterns, in various clinical scenarios and populations, and when measured repeatedly over time.
Descripción general del estudio
Estado
Activo, no reclutando
Intervención / Tratamiento
Descripción detallada
Allograft rejection remains a leading cause of kidney transplant failure, and standard-of-care monitoring detects it late.
Recently, combining dd-cfDNA with functional, immunological and clinical parameters has been shown to improve rejection detection under the Banff 2019 framework. However, the Banff 2022 revision formally recognized microvascular inflammation without DSA or C4d (MVI, DSA-negative, C4d-negative) and probable antibody-mediated rejection as distinct rejection phenotypes, raising the question of whether dd-cfDNA can help detecting these phenotypes. Its performance also remains unclear across the broader spectrum of Banff rejection phenotypes and injury patterns, when the complete diagnostic workup is unavailable, in the early post-transplant period, in specific populations, and when measured repeatedly over time.
The investigators therefore aim to evaluate the association between dd-cfDNA and Banff rejection phenotypes and its added diagnostic value to detect them, across the clinical situations in which the biomarker is used.
The study has three objectives:
- To assess the association between dd-cfDNA and Banff 2022 rejection phenotypes and injury patterns, including antibody-mediated, T cell-mediated and mixed rejection, borderline changes, probable antibody-mediated rejection and MVI, DSA-negative, C4d-negative, together with its relationship to the severity of the underlying lesions, with particular attention to microvascular inflammation.
- To assess the diagnostic value of dd-cfDNA, alone and within the integrative dd-cfDNA model, for the detection of biopsy-proven rejection as defined by the Banff 2022 classification, and beyond standard-of-care monitoring.
- To assess whether this performance is maintained across clinical scenarios and populations, including incomplete diagnostic workup, the first month post-transplant, delayed graft function, and specific subpopulations.
Secondarily, the investigators aim to assess whether serial dd-cfDNA improves the detection of rejection, and its prognostic value for death-censored allograft failure.
Tipo de estudio
De observación
Inscripción (Estimado)
5000
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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Berlin, Alemania
- Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin
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São Paulo, Brasil
- Nephrology Division, Hospital do Rim, Fundação Osvaldo Ramos, Federal University of São Paulo, São Paulo, Brazil
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Leuven, Bélgica
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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Seoul, Corea del Sur
- Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Barcelona, España
- Translational Nephrology and Kidney Transplant Research Laboratory, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
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California
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Los Angeles, California, Estados Unidos, 90048
- Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Los Angeles, California, Estados Unidos, 90048
- Department of Pediatrics, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
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Los Angeles, California, Estados Unidos, 90095
- Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Florida
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Tampa, Florida, Estados Unidos, 33606
- Department of Nephrology, Tampa General Hospital, Tampa, FL, USA
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA, USA
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Missouri
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St Louis, Missouri, Estados Unidos, 63110
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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St Louis, Missouri, Estados Unidos, 63110
- Division of Pediatric Nephrology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA
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New York
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New York, New York, Estados Unidos, 10065
- Division of Nephrology, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, USA
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Ohio
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Cleveland, Ohio, Estados Unidos, 44195-0001
- Cleveland Clinic, 2050 East 96th Street, Cleveland, OH
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Texas
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Dallas, Texas, Estados Unidos, 75390-8856
- Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Utah
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Murray, Utah, Estados Unidos, 84107
- Transplant Services, Intermountain Medical Center, Murray, UT, USA
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Salt Lake City, Utah, Estados Unidos, 84132
- Division of Nephrology, Department of Medicine, University of Utah Health, Salt Lake City, UT, USA
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Virginia
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Richmond, Virginia, Estados Unidos, 23219
- Division of Nephrology, Virginia Commonwealth University, Richmond, VA, USA
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53705
- Department of Medicine, Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
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Paris, Francia
- Hopital Necker
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Paris, Francia, 75015
- Department of Nephrology and Dialysis, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
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Paris, Francia
- 11- Pediatric Nephrology Department, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
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Paris, Francia
- Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris;
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Toulouse, Francia
- Department of Nephrology-Dialysis-Transplantation, CHU de Toulouse, Toulouse, France
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Geneva, Suiza, 1205
- Service de Néphrologie, Département de Médecine, Hôpitaux Universitaires de Genève, Geneva, Switzerland
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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
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Método de muestreo
Muestra no probabilística
Población de estudio
Kidney transplant recipients of all age and sexes with at least one kidney biopsy performed concurrently with dd-cfDNA measurement.
Descripción
Inclusion Criteria:
- Recipients transplanted from a deceased or living donor
- Kidney allograft biopsy concomitantly with dd-cfDNA measurement
- Written informed consent at the time of transplantation for inclusion the center database
Exclusion Criteria:
- Combined organ transplantation
- Pregnant women
- Grafts from monozygotic twins
- Recipient of a bone marrow transplant
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
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
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French Cohort
Necker and Saint Louis Hospitals Kidney Transplant Recipients Cohorts
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Cell-free DNA (cfDNA) is fragmented extracellular DNA released in the bloodstream from cells undergoing apoptosis or necrosis.
In transplantation, donor-derived cfDNA (dd-cfDNA) is detected in the blood of kidney recipients and has been proposed as a noninvasive biomarker to detect rejection.
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External Validation Cohort
Multinational cohort comprising transplant centers across Europe, North America, South America and Asia (see involved transplant centres in contacts and locations).
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Cell-free DNA (cfDNA) is fragmented extracellular DNA released in the bloodstream from cells undergoing apoptosis or necrosis.
In transplantation, donor-derived cfDNA (dd-cfDNA) is detected in the blood of kidney recipients and has been proposed as a noninvasive biomarker to detect rejection.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Allograft active injury
Periodo de tiempo: Periprocedural (At time of biopsy)
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Antibody-mediated rejection (active or chronic active) T cell-mediated rejection (active or chronic active) Mixed rejection Microvascular Inflammation, DSA-negative, C4d-negative Probable AMR
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Periprocedural (At time of biopsy)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Allograft loss
Periodo de tiempo: Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
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Return to dialysis or re-transplantation
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Rate of participants reaching graft loss between transplantation and last follow up (up to 10 years post-transplant)
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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.
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)
15 de junio de 2024
Finalización primaria (Estimado)
1 de diciembre de 2026
Finalización del estudio (Estimado)
31 de diciembre de 2026
Fechas de registro del estudio
Enviado por primera vez
24 de agosto de 2026
Primero enviado que cumplió con los criterios de control de calidad
3 de septiembre de 2026
Publicado por primera vez (Actual)
4 de septiembre de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
4 de septiembre de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
3 de septiembre de 2026
Última verificación
1 de septiembre de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- VALIDATE
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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. .