Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection

NCT04897438 | Completed

• 1 other identifier: CHA-NTX-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Patients after kidney transplantation who develop donor-specific antibodies (DSA) are at high risk for antibody-mediated rejection (ABMR). Donor-derived cell-free DNA (dd-cfDNA) levels have been shown to be increased in patients with active or chronic active ABMR. This study aims to evaluate if repeated analysis of dd-cfDNA in patients with DSA and kidney allograft biopsy which is triggered by increased levels of dd-cfDNA can lead to early diagnosis of active or chronic active ABMR among these patients.

Conditions

Kidney Transplant Rejection; Antibody-mediated Rejection; Kidney Transplant Failure

Outcome Measures

Primary Outcomes (1)

• Time from study inclusion to diagnosis of antibody-mediated rejection

  Time from study inclusion date to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection

  12 months after inclusion

Secondary Outcomes (22)

• Sensitivity of absolute dd-cfDNA for detection of ABMR

  12 Months

• Specificity of absolute dd-cfDNA for detection of ABMR

  12 Months

• Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR

  12 Months

• Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR

  12 Months

• Sensitivity of combined dd-cfDNA criterion for detection of ABMR

  12 Months

Study Arms (2)

Intervention

EXPERIMENTAL

Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. If absolute levels of dd-cfDNA are \> 50 copies/ml, the patients receive a kidney allograft biopsy. Additionally, kidney allograft biopsies are performed according to standard of care as determined by the treating physicians.

Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels

Control

NO INTERVENTION

Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. These measurements are not used to guide kidney allograft biopsies. Those are performed according to standard of care as determined by the treating physicians.

Interventions

Kidney allograft biopsy depending on donor-derived cell-free DNA levels PROCEDURE

Kidney allograft biopsy is performed, when absolute levels of donor-derived cell-free DNA are above 50 copies/ml

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients 18 years or older
• patients provided written informed consent
• patients after kidney transplantation
• functioning kidney allograft, at least after 180 days after last transplantation
• estimated glomerular filtration rate above 20 ml/min/1.73m\^2
• detection of DSA

You may not qualify if:

• patients younger than 18 years
• patients unable or did not provide written informed consent
• pregnant or breastfeeding persons
• patients with increased bleeding risk
• patients with multi-organ transplantation
• patients who underwent kidney allograft biopsy after first detection of DSA
• biopsy-proven antibody-mediated rejection
• participation in another interventional clinical trial

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité-Universitätsmedizin

Berlin, 10117, Germany

Location

Related Publications (2)

• Akifova A, Budde K, Amann K, Buettner-Herold M, Choi M, Oellerich M, Beck J, Bornemann-Kolatzki K, Schutz E, Bachmann F, Halleck F, von Hoerschelmann E, Koch N, Schrezenmeier E, Seelow E, Waiser J, Zukunft B, Eckardt KU, Halbritter J, Kettritz R, Del Moral CL, Lachmann N, Stauch D, Niemann M, Schmidt D, Halloran PF, Osmanodja B. Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial. Nephrol Dial Transplant. 2025 Jun 30;40(7):1384-1395. doi: 10.1093/ndt/gfae282.

  PMID: 39673311 DERIVED

• Oellerich M, Budde K, Osmanodja B, Bornemann-Kolatzki K, Beck J, Schutz E, Walson PD. Donor-Derived Cell-free DNA for Personalized Immunosuppression in Renal Transplantation. Ther Drug Monit. 2023 Feb 1;45(1):20-25. doi: 10.1097/FTD.0000000000001023.

  PMID: 36127770 DERIVED

Study Officials

• Klemens Budde, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Physician, Department of Nephrology and Medical Intensive Care

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 21, 2021
• Study Start: June 1, 2021
• Primary Completion: July 18, 2023
• Study Completion: September 9, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)