TY - JOUR
T1 - Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry
AU - Patry, Christian
AU - Sauer, Lukas D.
AU - Sander, Anja
AU - Krupka, Kai
AU - Fichtner, Alexander
AU - Brezinski, Jolanda
AU - Geissbühler, Yvonne
AU - Aubrun, Elodie
AU - Grinienko, Anna
AU - Strologo, Luca Dello
AU - Haffner, Dieter
AU - Oh, Jun
AU - Grenda, Ryszard
AU - Pape, Lars
AU - Topaloğlu, Rezan
AU - Weber, Lutz T.
AU - Bouts, Antonia
AU - Kim, Jon Jin
AU - Prytula, Agnieszka
AU - König, Jens
AU - Shenoy, Mohan
AU - Höcker, Britta
AU - Tönshoff, Burkhard
N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This study was funded by Novartis, Basel, Switzerland. The authors received funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), and The German Society for Paediatric Nephrology (GPN) and by grants from the pharmaceutical companies Astellas and Novartis. Publisher Copyright: © 2022, The Author(s).
PY - 2022/10/20
Y1 - 2022/10/20
N2 - Background: Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. Methods: In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). Results: Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. Conclusions: In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. Graphical abstract: [Figure not available: see fulltext.].
AB - Background: Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far. Methods: In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554). Results: Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable. Conclusions: In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation. Graphical abstract: [Figure not available: see fulltext.].
KW - Clinical trial design
KW - Emulated cohorts
KW - Pediatric kidney transplantation
KW - Real-World Data
UR - http://www.scopus.com/inward/record.url?scp=85140313464&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00467-022-05777-x
DO - https://doi.org/10.1007/s00467-022-05777-x
M3 - Article
C2 - 36264431
SN - 0931-041X
JO - Pediatric nephrology (Berlin, Germany)
JF - Pediatric nephrology (Berlin, Germany)
ER -