Dataset Information

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.

ABSTRACT:

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 m² P = 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. A higher resolution version of the Graphical abstract is available as Supplementary information.

SUBMITTER: Patry C

PROVIDER: S-EPMC9584233 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.

Patry Christian C Sauer Lukas D LD Sander Anja A Krupka Kai K Fichtner Alexander A Brezinski Jolanda J Geissbühler Yvonne Y Aubrun Elodie E Grinienko Anna A Strologo Luca Dello LD Haffner Dieter D Oh Jun J Grenda Ryszard R Pape Lars L Topaloğlu Rezan R Weber Lutz T LT Bouts Antonia A Kim Jon Jin JJ Prytula Agnieszka A König Jens J Shenoy Mohan M Höcker Britta B Tönshoff Burkhard B

Pediatric nephrology (Berlin, Germany) 20221020 5

<h4>Background</h4>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.<h4>Methods</h4>In this multicenter comparative analysis, we emulated the control cohort ...[more]

PMID: 36264431

Similar Datasets

Project description:BackgroundImmunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited.ObjectiveThe aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals.MethodsAdults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not.ResultsA total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history.ConclusionsTixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection.

Project description:BackgroundGlucose metabolism after kidney transplantation (KT) is highly dynamic with the first post-transplantation year being the most critical period for new-onset diabetes after transplantation (NODAT) occurrence. The present study aimed to analyze dynamics of glucose metabolism and report incidence/risk factors of abnormal glycemic state during the first year after KT in children.MethodsTwenty-one consecutive freshly transplanted pediatric kidney transplant recipients (KTRs) were assessed for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) weekly for 4 weeks, then every 3 months for 1 year.ResultsInterpretation of OGTT test showed normal glucose tolerance (NGT) in 6 patients (28.6%) while 15 (71.4%) experienced impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at any time point of monitoring. Seven patients had NODAT, for which three needed insulin therapy. Hyperglycemia onset was 7.8 ± 13.12 weeks (median (range) = 1 (0-24) week) after KT. Percent of patients with abnormal OGTT was significantly more than that of IFG (38.1% vs. 71.4%, p = 0.029). Patients with abnormal glycemic state had significantly elevated trough tacrolimus levels at 6 months (p = 0.03). Glucose readings did not correlate with steroid doses nor rejection episodes while positively correlating with tacrolimus doses at 3 months (p = 0.02, CC = 0.73) and 6 months (p = 0.01, CC = 0.63), and negatively correlating with simultaneous GFR at 9 months (p = 0.04, CC = - 0.57).ConclusionsUp to two thirds of pediatric KTRs (71.4%) experienced abnormal glycemic state at some point with peak incidence within the first week up to 6 months after KT. OGTT was a better tool for monitoring of glucose metabolism than FPG. Abnormal glycemic state was induced by tacrolimus and adversely affected graft function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Dataset Information

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.

Background

Methods

Results

Conclusions

Publications

Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets