Clinical trial NCT05306795: Development and Validation of a Comprehensive Classification Automation System for Kidney Allograft Biopsies
Official title: Development, Application, and Validation of a Comprehensive Classification Automation System for Allograft Precision Diagnostics in Adult and Pediatric Kidney Transplant Biopsies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplant Rejection
Pathology
Keywords: Banff classification
Kidney transplantation
Precision diagnostic
Automation
Lead sponsor: Paris Translational Research Center for Organ Transplantation
Sponsor class: OTHER
First posted: 2022-04-01
Enrollment: 4000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Kidney transplant recipients of all sexes recruited in observational studies performed in Europe and United States, with at least one kidney biopsy performed with all the relevant data to provide a reliable diagnosis according to the Banff classification (i.e., adequate biopsies without missing data for Banff lesion scores, donor-specific antibody status, and C4d staining).

Brief summary: Since 1991, the Banff classification has been the gold standard for defining antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR), thereby guiding the treatment and management of transplant recipients. Starting from a pure histological approach, the classification has moved over the past three decades towards an integrated precision diagnosis system, which encompasses other expertise, such as immunology, immunogenetic, other basic sciences, biostatistics, data science, and artificial intelligence The counterpart of this constant refinement is that Banff rules are becoming complex to follow, with numerous possible scenarios leading to a high degree of inter-observer variability and misclassifications, which may lead to therapeutic consequences.

The aims of this study are:

1. To integrate and decode all Banff rules and develop a computer-based application - the Banff Automation System - which provides automated and reproducible diagnoses
2. To validate the ability of the Banff Automation System to reclassify rejection diagnoses in multicenter cohort studies and clinical trials.

Detailed description: Despite considerable advances in the development of effective immunosuppressive therapies, allograft rejection remains the main cause of graft loss after kidney transplantation. Since 1991, the Banff classification has been the gold standard for defining antibody-mediated rejection (AMR) and T-cell mediated rejection (TCMR), thereby guiding the treatment and management of transplant recipients. Starting from a pure histological approach, the classification has moved over the past three decades towards an integrated precision diagnosis system, which encompasses other expertise, such as immunology, immunogenetic, other basic sciences, biostatistics, data science, and artificial intelligence The counterpart of this constant refinement is that Banff rules are becoming complex to follow, with numerous possible scenarios leading to a high degree of inter-observer variability and misclassifications, which may lead to therapeutic consequences. Hence, international transplant societies and regulatory agencies urgently appealed for a more comprehensible and reproducible classification, required for decision-making process and reliable surrogate endpoints, to further improve patients care and drug development.

The aims of this study are:

1. To integrate and decode all Banff rules and develop a computer-based application - the Banff Automation System - which provides automated and reproducible diagnoses
2. To validate the ability of the Banff Automation System to reclassify rejection diagnoses in multicenter cohort studies and clinical trials.

Based on the results, the investigators will provide a comprehensive, user-friendly, and open-access online application which might improve reproducibility and precision of biopsies' diagnoses, thereby reducing misclassifications, and path the way to standardize histology-based endpoints in observational studies and clinical trials, and post-transplant diagnostic and therapeutic's management of kidney transplant recipients.

Eligibility criteria: Inclusion Criteria:

* Kidney transplant recipients
* At least one kidney transplant biopsy performed, assessed with the Banff classification

Exclusion Criteria:

* Inadequate biopsy according to the Banff classification (number of glomeruli inferior less than seven)
* Missing data for Banff lesion scores
* Missing data for donor-specific antibody status
* Missing data for C4d (degradation product of the classic complement pathway) staining

Primary outcomes:
measure: Rejection-related diagnoses reclassified by the computer-based tool
timeFrame: 1 day (At time of a kidney allograft biopsy)
Secondary outcomes:
measure: Graft survival
timeFrame: 24 months post-kidney allograft biopsy
Other outcomes:
Locations:
city: Paris
country: France
facility: Paris Translational Centre for Organ Transplantation
state: Île-de-France
Study officials:
affiliation: Paris Translational Centre for Organ Transplantation
name: Alexandre Loupy, MD, PhD
role: STUDY_DIRECTOR
References:
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