Evaluation of the Efficacy of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients"

Официальное название

Randomized Controlled Multicenter Trial to Evaluate the Efficacy and Safety of Dd-cfDNA in Routine Patient Care in Kidney Transplant Recipients

Обзор

The investigator hypothesizes that the combined use of (1) Donor-derived cell-free DNA (dd-cfDNA) in peripheral blood predicting anti-donor immunological activation or quiescence (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive biopsy and less induced risk surveillance by allograft protocol biopsies to assess allograft rejection in clinically stable kidney transplant patients. In addition, the evaluation of the transcriptional changes in tissue samples in selected patients using automated processing of digital slide images and intragraft gene expression profiles will provide a better diagnosis of the rejection mechanisms to provide the best therapeutic approach as compared to current clinical practice. We therefore propose a French, multicenter, prospective randomized trial comparing two strategies of follow-up: in the first group, a biopsy is performed at M3, M12 and for clinical indication whenever considered necessary by the clinician during the first 18 months of follow-up after transplant. In the second group, patients will have the same follow-up as in the first group, but reports providing dd-cfDNA results and relevant medical parameters will be provided to the physician to help him in the decision to perform a biopsy or not.

Подробное описание

The main objective of the study is to assess whether the use of donor-derived cell-free DNA (dd-cfDNA) as an immunological biomarker combined with clinical data to decrease the number of allograft biopsies during the first 18 months after transplantation.

500 new transplanted patients in 6 French clinical transplant sites will be included in the prospective multicenter AI-CARE trial. Recruitment of patients will start on the day of transplantation (or 8 days before for transplantations with living donor) and data/samples collected at 3 months and 12 months after transplantation and during visits for clinical indication within the first 18 months of follow-up. Realization of all the acts for the research are representing the usual medical practice (Standard Of Care: SOC) except one additional blood sample for dd-cfDNA analyses that will be collected and analyzed specifically for the research. The paraffin-embedded core dedicated to SOC histology will be used for gene expression profiling and digital pathology imaging after SOC procedures.

Using the newest information derived from dd-cfDNA analyses combined with clinical data, dd-cfDNA will allow us to identify kidney transplant patients at low- and high-risk of rejection.

using non-invasive dd-cfDNA levels combined with clinical data, preventing unnecessary allograft biopsies which are invasive, with and present a potential risk of complications for the patients and costly burden to the healthcare

Вмешательства

• Биопрепарат dd-cfDNA-guided
  In groups I and II, the blood sample for dd-cfDNA assay will be taken on D0, just prior to transplantation, for all patients. in addition, for patients following a dd-cf DNA-guided strategy based on dd-cf DNA ; samples for dd-cf DNA assay will be taken at M3 and M12 visits and at visits for clinical indication (5 maximum) and the blood will be sent to the PARCC technical platform of INSERM UMR 970. By combining the dd-cfDNA level and relevant medical data, an integration report will be sent to

Первичные конечные точки

• compare levels of eGFR measured by CKD-EPI equation in both arms [Срок оценки: 18 months]

Вторичные конечные точки (11)

• modification of the immunosuppression treatment [Срок оценки: 18 months]
• graft survival rates [Срок оценки: 18 months]
• biopsy-proven rejections [Срок оценки: 18 months]
• incidence of death [Срок оценки: 18 months]
• probability of kidney allograft rejection measured by gene expression in the biopsy tissue [Срок оценки: 18 months]
• quantity of lesion patterns between both groups [Срок оценки: 18 months]
• compare health care expenses between both groups [Срок оценки: 18 months]
• compare EQ-5D-5L questionnaire answers between both group [Срок оценки: 18 months]
• compare the PREMs questionnaire answer in dd-cfDNA-guided group [Срок оценки: 18 months]
• compare the Generalised Anxiety Disorder Assessment (GAD-7 ) questionnaire answer between both group [Срок оценки: 18 months]
• compare the visual analyse scale ( VAS ) questionnaire answer between both group [Срок оценки: 18 months]

Критерии участия

Критерии включения

• All men and women, age ≥18 years old.
• Subject must be a recipient of a non-combined renal transplant from a deceased or living donor. It can be a re transplantation after a graft loss of function or graft rejection
• Subject is willing and able to provide signed written informed consent and willing to comply with study procedures
• Women of Childbearing Potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.

Критерии исключения

• Subjects who are legally detained in an official institution or under legal protection
• Any condition that, in the opinion of the investigator, might interfere with the patient 's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient
• History of multi-organ transplant (interference with rejection natural history).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 6 центров

• Georges Pompidou European Hospital — Paris
• Hôpital Necker-Enfants Malades — Paris
• AP-HP - Hôpital Tenon — Paris
• CHU Toulouse — Toulouse
• Hopital Saint Louis — Paris
• Hôpital de la Salpêtrière hôpital à Paris — Paris

Идентификаторы

NCT: NCT06406179 · APHP231641

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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