A continued method performance monitoring approach for the determination of pediatric renin samples – application within a European clinical trial

Abstract

BackgroundPlasma renin levels were determined in the academia-driven, EU-funded “Labeling of Enalapril from Neonates up to Adolescents” (LENA) project to evaluate its role in pediatric heart failure. Quality-controlled bioanalysis is crucial to ensure reliable data generation. However, a comprehensive bioanalytical quality control (QC) concept to monitor the method performance within an academic environment was lacking.MethodsThus, a QC concept was designed encompassing regulatory guidance, international recommendations and current scientific discussions. The concept included (1) a system-suitability test, (2) verification of single bioanalytical runs by calibration curve performance and evaluation of QCs, (3) assessment of the inter-run accuracy according to Clinical Laboratory Standards Institute (CLSI) guideline, (4) monitoring of reproducibility by pediatric incurred samples, (5) blank-sample analysis and (6) participation in interlaboratory testing.ResultsThe concept was successfully applied to the academic project. About 11% of single runs were identified as invalid and triggered a re-analysis of unknown samples being included in those runs. The usefulness of the customized inter-run monitoring was demonstrated and proved the good accuracy from the first to the last run. All 147 reanalyzed incurred sample pairs complied with regulatory requirements.ConclusionsThe regulatory complied QC concept was customized for the demands of academia-driven pediatric trials and contributed to the reliable quantification of 965 pediatric renin samples.

Population pharmacokinetics of lisinopril in hypertensive children and adolescents with normal to mildly reduced kidney function

“…3,4,11 Enalapril and lisinopril are 2 commonly used ACE inhibitors, with enalapril having been the first to receive Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval based on data from the LENA project. [11][12][13] However, there are limited studies on the use of lisinopril. 1,14,15 Soffer et al (2003) investigated the dose-response relationship of lisinopril in 115 hypertensive children between the ages of 6 and 16 years, with doses ranging from 0.02 to 0.61 mg kg À1 .…”

“…Angiotensin‐converting enzyme (ACE) inhibitors are the preferred treatment for primary and secondary pHTN due to their effectiveness in reducing blood pressure (BP) in a dose‐dependent manner, as well as their well‐tolerated nature and additional nephroprotective effect 3,4,11 . Enalapril and lisinopril are 2 commonly used ACE inhibitors, with enalapril having been the first to receive Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval based on data from the LENA project 11–13 . However, there are limited studies on the use of lisinopril 1,14,15 .…”