清宣止咳颗粒治疗儿童流感(风热犯肺证)多中心、随机、对照研究

A multicenter,randomized,controlled study on the treatment of pediatric influenza(wind-heat invading lung)with Qingxuan Zhike granules

目的评价清宣止咳颗粒改善儿童流感(风热犯肺证)咳嗽症状、缩短病程的有效性及临床应用的安全性。方法多中心、随机、对照临床试验。收集2023年4月至12月云南中医药大学第一附属医院等7家医院门诊流感患儿240例,采用区组随机方法,通过SAS软件将受试者随机分为对照组和试验组,2组间比较采用t检验、校正t检验及χ^(2)检验。对照组予磷酸奥司他韦颗粒,口服,2次/d。体重≤15 kg,30 mg/次;体重>15~23 kg,45 mg/次;体重>23~40 kg,60 mg/次;体重>40 kg,75 mg/次;若年龄≥13岁,75 mg/次。试验组在对照组基础上加用清宣止咳颗粒,口服,3次/d。1~3岁,每次1/2包;>3~6岁,每次3/4包;>6~14岁,每次1包。疗程:治疗5 d,停药观察2 d。观察2组患儿咳嗽疗效、退热疗效、临床痊愈率、临床痊愈时间、加拿大急性呼吸道疾病和流感量表(CARIFS)评分、中医证候疗效、并发症发生率及不良反应发生情况。结果最终纳入统计232例,其中试验组115例,对照组117例。治疗前后,试验组CARIFS咳嗽评分与对照组比较差异均无统计学意义(均P>0.05);治疗后试验组CARIFS咳嗽评分变化值[(-1.00±0.91)分]与对照组[(-0.75±0.98)分]比较,差异有统计学意义(t=-1.995,P=0.047);治疗后试验组中医证候咳嗽评分变化值[(-1.69±1.51)分]与对照组[(-0.97±1.63)分]比较,差异有统计学意义(t′=-0.035,P=0.001)。试验组完全退热时间[(44.82±22.72)h]短于对照组[(51.35±27.07)h],2组比较差异有统计学意义(t=-1.966,P=0.050)。发热维度评分显示,试验组CARIFS症状维度发热评分与时间的曲线下面积为4.40±2.42,对照组为5.12±2.44,2组比较差异有统计学意义(t=-2.252,P=0.025)。试验组临床痊愈率为93.91%(108/115),对照组临床痊愈率为92.31%(108/117),2组比较差异无统计学意义(χ^(2)=0.233,P>0.05)。试验组临床痊愈时间[(2.93±1.21)d]短于对照组[(3.29±1.15)d],2组比较差异有统计学意义(t=-2.279,P=0.024)。治疗后试验组中医证候评分变化值[(-12.00±4.13)分]与对照组[(-10.85±4.31)分]比较差异有统计学意义(t′=-2.067,P=0.040)。2组均未发生并发症,不良事件发生率比较差异无统计学意义(χ^(2)=1.299,P>0.05)。结论清宣止咳颗粒联合磷酸奥司他韦可有效改善儿童流感伴随的咳嗽症状,缩短退热时间和病程,改善中医证候评分,安全性良好。

Objective To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza(wind-heat invading lung)in children.Methods In this multicenter,randomized,controlled clinical trial,a total of 240 outpatient influenza patients from 7 hospitals,including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine,from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test,corrected t test andχ^(2) test.Subjects in the control group were given Oseltamivir phosphate granules,orally,twice a day(weight≤15 kg,30 mg/time;weight>15-23 kg,45 mg/time;weight>23-40 kg,60 mg/time;weight>40 kg,75 mg/time;age≥13 years,75 mg/time).In addition to Oseltamivir phosphate granules,subjects in the experimental group were also given Qingxuan Zhike granules,orally,3 times a day(1-3 years old,1/2 bag each time;>3-6 years old,3/4 bag each time;>6-14 years old,1 bag each time).After 5 days of treatment,the medication was suspended for 2 days.The effect of cough,antipyretic effect,clinical recovery rate,clinical recovery time,Canadian Acute Respiratory Illness and Flu Scale(CARIFS)score,traditional Chinese medicine(TCM)syndrome effect,complication rate,and adverse reactions were evaluated between the two groups.Results Finally,232 cases were included in the study,including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment,there were no significant difference in CARIFS cough score between the experimental group and the control group(all P>0.05).After treatment,the change in CARIFS cough score in the experimental group[(-1.00±0.91)scores]was significantly higher than that in the control group[(-0.75±0.98)scores](t=-1.995,P=0.047).After treatment,the change in TCM syndrome cough score in the experimental group[(-1.69±1.51)scores]was significantly higher than that in the control group[(-0.97±1.63)scores](t′=-0.035,P=0.001).The time of complete regression of fever in the experimental group[(44.82±22.72)h]was shorter than that in the control group[(51.35±27.07)h],and the difference between the two groups was statistically significant(t=-1.966,P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42,while that in the control group was 5.12±2.44,and the difference between the two groups was statistically significant(t=-2.252,P=0.025).The clinical recovery rate was 93.91%(108/115)in the experimental group and 92.31%(108/117)in the control group,and there was no significant difference between the two groups(χ^(2)=0.233,P>0.05).The clinical recovery time in the experimental group[(2.93±1.21)d]was shorter than that in the control group[(3.29±1.15)d],and the difference between the two groups was statistically significant(t=-2.279,P=0.024).After treatment,there was a significant difference in TCM syndrome score variation between the experimental group[(-12.00±4.13)scores]and the control group[(-10.85±4.31)scores](t′=-2.067,P=0.040).No complication occurred in both groups,and there was no significant difference in the incidence of adverse events between the two groups(χ^(2)=1.299,P>0.05).Conclusions Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children,shorten the time and course of fever,and improve the TCM syndrome score;thus,they are safe in clinical application.