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

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.

Evaluation of the warming sensation, acceptability, and local tolerability of an acetylcysteine oral solution containing the flavoring agent IFF flavor 316282 in the treatment of productive cough
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OBJECTIVE: This open-label study sought to evaluate the warming sensation produced by IFF flavor 316282 in an acetylcysteine oral solution in subjects with productive cough. MATERIALS: 2% ace-tylcysteine oral solution (200 mg per 10 mL) containing IFF flavor 316282. METHODS: Subjects (N = 57; mean age 38.7 years; 58% female) with a productive cough lasting < 7 days and rated as mild to moderate in severity received 10 mL of study product. Warming sensation intensity was assessed using a 100-mm visual analog scale, its onset and duration using stopwatches, its acceptability using a 9-point scale (from "dislike extremely" to "like extremely") and the taste, texture, and overall acceptability of the solution using 5-point scales (from "unacceptable" to "excellent"). RESULTS: 53 (93.0%) subjects perceived a warming sensation within 10 minutes of swallowing the solution; median onset was ~ 14 seconds, and median duration was ~ 2.8 minutes. Warming sensation intensity increased from baseline by a mean of 29.2 mm when evaluated 60 seconds after ingestion. 30 subjects (52.6%) thought the warming sensation was "just about right"; 25 (43.9%) considered it "too weak" or "much too weak." Most subjects had positive overall ratings ("fair," "good," or "excellent") of the taste (79.0%), texture (96.5%), and solution (91.2%). No treatment-emergent adverse events were reported, and no evidence of oral mucosal irritation was found. CONCLUSION: The addition of IFF flavor 316282 to a 2% acetylcysteine oral solution produced a warming sensation with rapid onset and relatively short duration, which the majority of subjects found acceptable.
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