Clinical trial NCT04897438: Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection
Official title: Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection in Kidney Transplant Recipient with Donor-specific Antibodies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Transplant Rejection
Antibody-mediated Rejection
Kidney Transplant Failure
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2021-05-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility 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

Primary outcomes:
measure: Time from study inclusion to diagnosis of antibody-mediated rejection
timeFrame: 12 months after inclusion
Secondary outcomes:
measure: Sensitivity of absolute dd-cfDNA for detection of ABMR
timeFrame: 12 Months
measure: Specificity of absolute dd-cfDNA for detection of ABMR
timeFrame: 12 Months
measure: Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR
timeFrame: 12 Months
measure: Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR
timeFrame: 12 Months
measure: Sensitivity of combined dd-cfDNA criterion for detection of ABMR
timeFrame: 12 Months
measure: Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months
timeFrame: 12 Months
measure: Clinical Outcome - eGFR 24 Months
timeFrame: 24 Months
measure: Clinical Outcome - albuminuria 12 Months
timeFrame: 12 Months
measure: Clinical Outcome - albuminuria 24 Months
timeFrame: 24 Months
measure: Clinical Outcome - Death-censored Graft Failure 12 Months
timeFrame: 12 Months
measure: Clinical Outcome - Death-censored Graft Failure 24 Months
timeFrame: 24 Months
measure: Clinical Outcome - Mortality 12 Months
timeFrame: 12 Months
measure: Clinical Outcome - Mortality 24 Months
timeFrame: 24 Months
measure: Clinical Outcome - Severe Infection 12 Months
timeFrame: 12 Months
measure: Clinical Outcome - Severe Infection 24 Months
timeFrame: 24 Months
measure: Adverse Events of Kidney Transplant Biopsy
timeFrame: 12 Months
measure: Rate of ABMR
timeFrame: 12 Months
measure: DSA Levels 0 Months
timeFrame: at inclusion
measure: DSA Levels 12 Months
timeFrame: 12 months
measure: DSA Levels 24 Months
timeFrame: 24 months
measure: Immunosuppressive Regimen
timeFrame: 24 months
measure: Time from first DSA occurrence to diagnosis of antibody-mediated rejection
timeFrame: 12 months after inclusion
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Klemens Budde, MD
role: PRINCIPAL_INVESTIGATOR
References: