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

Kidney Transplant Rejection Clinical Trial

— cfDNA-DSA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04897438
• Other study ID #: CHA-NTX-001
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 1, 2021
• Est. completion date: September 1, 2024

Study information

• Verified date: September 2023
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: September 1, 2024
• Est. primary completion date: July 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antibody-mediated Rejection
• Kidney Transplant Failure
• Kidney Transplant Rejection

Intervention

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

Locations

Country	Name	City	State
Germany	Charité-Universitätsmedizin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Sensitivity of absolute dd-cfDNA for detection of ABMR	Sensitivity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Secondary	Specificity of absolute dd-cfDNA for detection of ABMR	Specificity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Secondary	Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR	ROC analysis for dd-cfDNA to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Secondary	Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR	Sensitivity of dd-cfDNA increase of > 25% to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Secondary	Sensitivity of combined dd-cfDNA criterion for detection of ABMR	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.	12 Months
Secondary	Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months	Difference between eGFR decline after 12 months between control group and intervention group.	12 Months
Secondary	Clinical Outcome - eGFR 24 Months	Difference between eGFR decline after 24 months between control group and intervention group.	24 Months
Secondary	Clinical Outcome - albuminuria 12 Months	Difference between albuminuria after 12 months between control group and intervention group.	12 Months
Secondary	Clinical Outcome - albuminuria 24 Months	Difference between albuminuria after 24 months between control group and intervention group.	24 Months
Secondary	Clinical Outcome - Death-censored Graft Failure 12 Months	Difference in Death-censored Graft Failure after 12 months between control group and intervention group.	12 Months
Secondary	Clinical Outcome - Death-censored Graft Failure 24 Months	Difference in Death-censored Graft Failure after 24 months between control group and intervention group.	24 Months
Secondary	Clinical Outcome - Mortality 12 Months	Difference in Mortality after 12 months between control group and intervention group.	12 Months
Secondary	Clinical Outcome - Mortality 24 Months	Difference in Mortality after 24 months between control group and intervention group.	24 Months
Secondary	Clinical Outcome - Severe Infection 12 Months	Difference in occurence of severe infections (hospitalization, organ failure, death) during 12 months between control group and intervention group.	12 Months
Secondary	Clinical Outcome - Severe Infection 24 Months	Difference in occurence of severe infections (hospitalization, organ failure, death) during 24 months between control group and intervention group.	24 Months
Secondary	Adverse Events of Kidney Transplant Biopsy	Occurence of Complications from Kidney Transplant Biopsies, including Duration and potential therapy to treat the adverse event.	12 Months
Secondary	Rate of ABMR	Number of biopsy proven active or chronic active ABMR in the cohort.	12 Months
Secondary	DSA Levels 0 Months	Mean fluorescence intensity of immunodominant DSA	at inclusion
Secondary	DSA Levels 12 Months	Mean fluorescence intensity of immunodominant DSA at 12 months	12 months
Secondary	DSA Levels 24 Months	Mean fluorescence intensity of immunodominant DSA at 24 months	24 months
Secondary	Immunosuppressive Regimen	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.	24 months
Secondary	Time from first DSA occurrence to diagnosis of antibody-mediated rejection	Time from first DSA occurrence to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection	12 months after inclusion