Multicentre randomised controlled trial protocol of urine CXCL10 monitoring strategy in kidney transplant recipients.Ho, J., Sharma, A. et al. (2019).
BMJ Open; 9(4): e024908.
To determine if early treatment of rejection, as detected by urine CXCL10 and confirmed by CXCL10-guided biopsy, will improve kidney allograft outcomes.
Patients will be randomized to either the control arm, which comprises usual care, or the intervention arm, which includes urine CXCL10 screening and a study biopsy to check for subclinical rejection.
Adult kidney transplant patients will be enrolled, but only those who also present with a high risk of rejection, defined as confirmed elevated urine CXCL10 level will be randomized (n=250) into this study. Patients will be randomized to either the control arm (n=125) or the intervention arm (n=125).
The primary outcomes will be assessed as death-censored graft loss; clinical biopsy-proven acute rejection; dnDSA development; subclinical chronic active TCMR or inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA); or subclinical tubulitis. Subclinical chronic active TCMR and tubulitis will be evaluated on the 12-month study exit biopsy in all randomised patients. Secondary outcomes will be measured as graft function evaluated by Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD eGFR), defined by change in graft function (6–12 months, slope and
This paper details the protocol for a multicentre randomised controlled trial. Urinary CXCL10 now has some evidence to support its use in identifying kidney recipients who would benefit from a transplant biopsy, by rising prior to creatinine. By catching subclinical acute rejection early, the authors speculate that transplant outcomes will be improved and have designed a large study to prove this. This study will be international and aims to randomise 250 kidney transplant recipients deemed to be at high risk of rejection due to elevated urine CXCL10 levels. An additional 170 patients at low risk of rejection will also be followed up. The power calculation makes allowance for 20% dropout. The method of randomisation will be by a central computer generation that is stratified for centre in randomly permuted blocks to maintain allocation concealment. The study cannot be blinded though as the study arm will have a transplant biopsy.
Protocol - QA not necessary
ClinicalTrials.gov - NCT03206801