Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial

ObjectiveTo evaluate the effectiveness and safety of Xiao’er Fengreqing Oral Liquid (XFOL) for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome) through a multi-center, randomized, double-blind, positive-controlled, non-inferiority clinical trial.MethodA total of 120 participants...

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Main Authors: Kai Liu, Lei Shi, Yi-Ke Song, Yu Du, Yi Yuan, Ze-Yang Shi, Jian-Ping Liu, Hui-Lan Liu, Zhao-Lan Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1625547/full
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author Kai Liu
Lei Shi
Yi-Ke Song
Yu Du
Yi Yuan
Ze-Yang Shi
Jian-Ping Liu
Hui-Lan Liu
Zhao-Lan Liu
author_facet Kai Liu
Lei Shi
Yi-Ke Song
Yu Du
Yi Yuan
Ze-Yang Shi
Jian-Ping Liu
Hui-Lan Liu
Zhao-Lan Liu
author_sort Kai Liu
collection DOAJ
description ObjectiveTo evaluate the effectiveness and safety of Xiao’er Fengreqing Oral Liquid (XFOL) for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome) through a multi-center, randomized, double-blind, positive-controlled, non-inferiority clinical trial.MethodA total of 120 participants (60 per group) will be randomized to receive either XFOL or Xiao’er Yanbian Granules (positive control) for 5 days. The primary outcome is the throat pain resolution rate and overall effective rate at Day 5, assessed via the Wong-Baker Faces Pain Rating Scale (WBS). Secondary outcomes include time to symptom onset/resolution, fever resolution time, and traditional Chinese medicine (TCM) syndrome scores. Safety assessments will monitor adverse events, vital signs, and laboratory parameters. Statistical analyses will follow a pre-specified plan, employing non-inferiority testing, survival analysis for time-to-event endpoints, and generalized estimating equations for repeated measures. Missing data will be handled using the last observation carried forward (LOCF) method for effectiveness endpoints, while safety analyses will rely on observed cases.ConclusionThis trial will provide rigorous evidence on the non-inferiority and safety profile of Fengreqing Oral Liquid, supporting its integration into pediatric care for acute upper respiratory infections. Adherence to a predefined statistical analysis plan ensures transparency and minimizes bias, ultimately guiding evidence-based clinical practice for TCM interventions.
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spelling doaj-art-e1ca394c3e854a81985a1c6d371bf6592025-08-20T03:51:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16255471625547Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trialKai Liu0Lei Shi1Yi-Ke Song2Yu Du3Yi Yuan4Ze-Yang Shi5Jian-Ping Liu6Hui-Lan Liu7Zhao-Lan Liu8Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaBusiness Analytics, University of Colorado Denver, Denver, CO, United StatesCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaThe Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, ChinaCentre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, ChinaObjectiveTo evaluate the effectiveness and safety of Xiao’er Fengreqing Oral Liquid (XFOL) for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome) through a multi-center, randomized, double-blind, positive-controlled, non-inferiority clinical trial.MethodA total of 120 participants (60 per group) will be randomized to receive either XFOL or Xiao’er Yanbian Granules (positive control) for 5 days. The primary outcome is the throat pain resolution rate and overall effective rate at Day 5, assessed via the Wong-Baker Faces Pain Rating Scale (WBS). Secondary outcomes include time to symptom onset/resolution, fever resolution time, and traditional Chinese medicine (TCM) syndrome scores. Safety assessments will monitor adverse events, vital signs, and laboratory parameters. Statistical analyses will follow a pre-specified plan, employing non-inferiority testing, survival analysis for time-to-event endpoints, and generalized estimating equations for repeated measures. Missing data will be handled using the last observation carried forward (LOCF) method for effectiveness endpoints, while safety analyses will rely on observed cases.ConclusionThis trial will provide rigorous evidence on the non-inferiority and safety profile of Fengreqing Oral Liquid, supporting its integration into pediatric care for acute upper respiratory infections. Adherence to a predefined statistical analysis plan ensures transparency and minimizes bias, ultimately guiding evidence-based clinical practice for TCM interventions.https://www.frontiersin.org/articles/10.3389/fphar.2025.1625547/fullpharyngitistonsillitisXiao’er Fengreqing oral Liquidrandomized controlled trialnon-inferiority designtrial protocol
spellingShingle Kai Liu
Lei Shi
Yi-Ke Song
Yu Du
Yi Yuan
Ze-Yang Shi
Jian-Ping Liu
Hui-Lan Liu
Zhao-Lan Liu
Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
Frontiers in Pharmacology
pharyngitis
tonsillitis
Xiao’er Fengreqing oral Liquid
randomized controlled trial
non-inferiority design
trial protocol
title Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
title_full Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
title_fullStr Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
title_full_unstemmed Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
title_short Xiao’er Fengreqing oral liquid versus Xiao’er Yanbian granules for pediatric acute pharyngitis/tonsillitis (external wind heat syndrome): protocol and statistical analysis plan for a multi-center, randomized, double-blind, active drug-controlled trial
title_sort xiao er fengreqing oral liquid versus xiao er yanbian granules for pediatric acute pharyngitis tonsillitis external wind heat syndrome protocol and statistical analysis plan for a multi center randomized double blind active drug controlled trial
topic pharyngitis
tonsillitis
Xiao’er Fengreqing oral Liquid
randomized controlled trial
non-inferiority design
trial protocol
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1625547/full
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