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Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection (cfDNA-DSA)

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ClinicalTrials.gov Identifier: NCT04897438
Recruitment Status : Active, not recruiting
First Posted : May 21, 2021
Last Update Posted : January 30, 2024
Sponsor:
Information provided by (Responsible Party):
Klemens Budde, Charite University, Berlin, Germany

Study Description
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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.

Condition or disease Intervention/treatment Phase
Kidney Transplant Rejection Antibody-mediated Rejection Kidney Transplant Failure Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection in Kidney Transplant Recipient With Donor-specific Antibodies
Actual Study Start Date : June 1, 2021
Actual Primary Completion Date : July 18, 2023
Estimated Study Completion Date : September 1, 2024

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Arms and Interventions
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Arm Intervention/treatment
Experimental: 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. 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
Kidney allograft biopsy is performed, when absolute levels of donor-derived cell-free DNA are above 50 copies/ml
No Intervention: Control
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.


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04897438


Locations
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Germany
Charité-Universitätsmedizin
Berlin, Germany, 10117
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
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Principal Investigator: Klemens Budde, MD Charite University, Berlin, Germany
More Information
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Responsible Party: Klemens Budde, Senior Physician, Department of Nephrology and Medical Intensive Care, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT04897438    
Other Study ID Numbers: CHA-NTX-001
First Posted: May 21, 2021    Key Record Dates
Last Update Posted: January 30, 2024
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No