Skip to main content
OpenTrials
Completed

NCT Number: NCT04897438

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Kidney Transplant Rejection Antibody-mediated Rejection Kidney Transplant Failure

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Charité-Universitätsmedizin

Berlin, 10117, Germany

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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

Primary outcomes

  1. Time from study inclusion to diagnosis of antibody-mediated rejection

    Time frame: 12 months after inclusion

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

Secondary outcomes

  1. Sensitivity of absolute dd-cfDNA for detection of ABMR

    Time frame: 12 Months

    Sensitivity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.

  2. Specificity of absolute dd-cfDNA for detection of ABMR

    Time frame: 12 Months

    Specificity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.

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

    Time frame: 12 Months

    ROC analysis for dd-cfDNA to predict the occurence of active or chronic active ABMR in patients with DSA.

  4. Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR

    Time frame: 12 Months

    Sensitivity of dd-cfDNA increase of > 25% to predict the occurence of active or chronic active ABMR in patients with DSA.

  5. Sensitivity of combined dd-cfDNA criterion for detection of ABMR

    Time frame: 12 Months

    Sensitivity of the combination of "dd-cfDNA increase of > 25%" OR "absolute dd-cfDNA > 50 copies/ml" to predict the occurence of active or chronic active ABMR in patients with DSA.

  6. Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months

    Time frame: 12 Months

    Difference between eGFR decline after 12 months between control group and intervention group.

  7. Clinical Outcome - eGFR 24 Months

    Time frame: 24 Months

    Difference between eGFR decline after 24 months between control group and intervention group.

  8. Clinical Outcome - albuminuria 12 Months

    Time frame: 12 Months

    Difference between albuminuria after 12 months between control group and intervention group.

  9. Clinical Outcome - albuminuria 24 Months

    Time frame: 24 Months

    Difference between albuminuria after 24 months between control group and intervention group.

  10. Clinical Outcome - Death-censored Graft Failure 12 Months

    Time frame: 12 Months

    Difference in Death-censored Graft Failure after 12 months between control group and intervention group.

  11. Clinical Outcome - Death-censored Graft Failure 24 Months

    Time frame: 24 Months

    Difference in Death-censored Graft Failure after 24 months between control group and intervention group.

  12. Clinical Outcome - Mortality 12 Months

    Time frame: 12 Months

    Difference in Mortality after 12 months between control group and intervention group.

  13. Clinical Outcome - Mortality 24 Months

    Time frame: 24 Months

    Difference in Mortality after 24 months between control group and intervention group.

  14. Clinical Outcome - Severe Infection 12 Months

    Time frame: 12 Months

    Difference in occurence of severe infections (hospitalization, organ failure, death) during 12 months between control group and intervention group.

  15. Clinical Outcome - Severe Infection 24 Months

    Time frame: 24 Months

    Difference in occurence of severe infections (hospitalization, organ failure, death) during 24 months between control group and intervention group.

  16. Adverse Events of Kidney Transplant Biopsy

    Time frame: 12 Months

    Occurence of Complications from Kidney Transplant Biopsies, including Duration and potential therapy to treat the adverse event.

  17. Rate of ABMR

    Time frame: 12 Months

    Number of biopsy proven active or chronic active ABMR in the cohort.

  18. DSA Levels 0 Months

    Time frame: at inclusion

    Mean fluorescence intensity of immunodominant DSA

  19. DSA Levels 12 Months

    Time frame: 12 months

    Mean fluorescence intensity of immunodominant DSA at 12 months

  20. DSA Levels 24 Months

    Time frame: 24 months

    Mean fluorescence intensity of immunodominant DSA at 24 months

  21. Immunosuppressive Regimen

    Time frame: 24 months

    Report of immunosuppressive medication at the following time points: 0,1,3,6,9,12,24 months, changes of medication, additional therapies such as plasmapheresis, or experimental therapies.

  22. Time from first DSA occurrence to diagnosis of antibody-mediated rejection

    Time frame: 12 months after inclusion

    Time from first DSA occurrence to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection

Sponsors and collaborators

Lead sponsor

Charite University, Berlin, Germany

Other

Registry information

Official study title

Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection in Kidney Transplant Recipient with Donor-specific Antibodies

Acronym: cfDNA-DSA

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
May 21, 2021
Registry last updated
Jan 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.