Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD): Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial

Abstract

Background: Enhance Access to Kidney Transplantation and Living Kidney Donation (EnAKT LKD) is a quality improvement intervention designed to enhance access to kidney transplantation and living kidney donation. We conducted a cluster-randomized clinical trial to evaluate the effect of the intervention versus usual care on completing key steps toward receiving a kidney transplant. Objective: To prespecify the statistical analysis plan for the EnAKT LKD trial. Design: The EnAKT LKD trial is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized, superiority, clinical trial. Randomization was performed at the level of the chronic kidney disease (CKD) programs (the “clusters”). Setting: Twenty-six CKD programs in Ontario, Canada. Participants: More than 10 000 patients with advanced CKD (ie, patients approaching the need for dialysis or receiving maintenance dialysis) with no recorded contraindication to receiving a kidney transplant. Methods: The trial data (including patient characteristics and outcomes) will be obtained from linked administrative health care databases (the “registry”). Stratified covariate-constrained randomization was used to allocate the 26 CKD programs (1:1) to provide the intervention or usual care from November 1, 2017, to December 31, 2021 (4.17 years). CKD programs in the intervention arm received the following: (1) support for local quality improvement teams and administrative needs; (2) tailored education and resources for staff, patients, and living kidney donor candidates; (3) support from kidney transplant recipients and living kidney donors; and (4) program-level performance reports and oversight by program leaders. Outcomes: The primary outcome is completing key steps toward receiving a kidney transplant, where up to 4 unique steps per patient will be considered: (1) patient referred to a transplant center for evaluation, (2) a potential living kidney donor begins their evaluation at a transplant center to donate a kidney to the patient, (3) patient added to the deceased donor transplant waitlist, and (4) patient receives a kidney transplant from a living or deceased donor. Analysis plan: Using an intent-to-treat approach, the primary outcome will be analyzed using a patient-level constrained multistate model adjusting for the clustering in CKD programs. Trial Status: The EnAKT LKD trial period is November 1, 2017, to December 31, 2021. We expect to analyze and report the results once the data for the trial period is available in linked administrative health care databases. Trial Registration: The EnAKT LKD trial is registered with the U.S. National Institute of Health at clincaltrials.gov (NCT03329521 available at https://clinicaltrials.gov/ct2/show/NCT03329521 ). Statistical Analytic Plan: Version 1.0 August 26, 2022.

Effect of a Novel Multicomponent Intervention to Improve Patient Access to Kidney Transplant and Living Kidney Donation

“…Trial data came mainly from linked administrative health care databases, including dialysis and transplant registries. We published the protocol (Supplement 1) and statistical plan (Supplement 2) before the outcome analysis, and changes to the protocol prior to this analysis are documented at ClinicalTrials.gov Identifier: NCT03329521 . The trial was designed, analyzed, and reported following recommended guidelines (eTables 1-4 in Supplement 3).…”

“…In prespecified additional analyses, we investigated the consistency of the estimated intervention effect in models that were (1) unadjusted for characteristics, (2) adjusted for additional baseline characteristics, and (3) unconstrained to examine intervention effects on each transition shown visually in eFigures 1A and 1B in Supplement 3. The intervention effect was also assessed on steps not specified as secondary outcomes (kidney transplant [from a living or deceased donor], deceased donor transplant, referral, and waitlisting); in follow-up truncated to March 16, 2020, the date when nearly all kidney transplant activity in Ontario stopped due to the COVID-19 pandemic; and in multiple subgroups . In another prespecified analysis, times to step completion were examined separately in each group along with other measures.…”

“…We published the protocol ( Supplement 1 ) and statistical plan ( Supplement 2 ) before the outcome analysis, and changes to the protocol prior to this analysis are documented at ClinicalTrials.gov Identifier: NCT03329521 . 5 , 11 The trial was designed, analyzed, and reported following recommended guidelines (eTables 1-4 in Supplement 3 ). 12 , 13 , 14 The Health Sciences Research Ethics Committee of Western University approved the trial to use a waiver of patient consent for participation (REB #108408).…”

“…Details are in the trial protocol and statistical plan ( Supplement 1 and Supplement 2 ). 5 , 11 Accounting for the correlation within clusters, the trial was designed to have at least 80% power to detect a between-group difference of 12 steps per 100 patient-years (assumed 23 steps per 100 patient-years in the usual-care group, 2-sided α = .05).…”

“…Details are in the statistical plan ( Supplement 2 ). 11 We performed the analyses using SAS statistical software (version 9.4; SAS Institute, Inc) and R statistical software (version 3.6, R Foundation). 30 The analysis was performed between October 2022 and March 2023, after outcome data for the entire trial period became available in the data sources used.…”