丙酸氟替卡松雾化吸入用混悬液在2~4岁哮喘儿童急性发作期的有效性和安全性多中心临床研究

Efficacy and safety of fluticasone propionate nebuliser suspension in acute attack of asthma children aged 2 to 4 years:A clinical multicenter study

目的观察丙酸氟替卡松雾化吸入用混悬液治疗2~4岁哮喘儿童急性发作的有效性和安全性。方法采用随机、活性药物对照、多中心临床研究设计,纳入10家医院于2022年6月至2023年2月的245例2~4岁哮喘急性发作的住院儿童,按照1.5∶1的比例随机分为丙酸氟替卡松雾化吸入用混悬液(简称雾化FP)组或雾化用布地奈德混悬液(简称雾化BUD组)。观察两组每日日间及夜间临床症状评分、呼吸指数评分及与基线的差值、其他哮喘缓解药物使用来评估有效性,以第3天日间临床症状评分与基线差值作为主要疗效指标,并进一步根据哮喘严重程度进行亚组分析。观察用药前后血常规、肝功能、心肌酶、肾功能、心电图的变化及不良事件发生率等评估安全性。最终239例完成5~7 d的研究。结果两组间主要疗效指标差异不具有统计学意义(P>0.05);雾化FP组第2天夜间临床症状评分与基线差值大于雾化BUD组(P<0.05);雾化FP组第4天日间临床症状评分大于雾化BUD组(P<0.05);其余时间点两组日间症状评分、夜间临床症状评分、呼吸指数评分及与基线差值差异均不具有统计学意义(P>0.05)。在合并应用全身性糖皮质激素的例数及次数上,雾化FP组与雾化BUD组间差异不具有统计学意义(P>0.05)。轻度哮喘发作患儿,雾化FP组第2、4天夜间临床症状评分与基线差值均大于雾化BUD组(P<0.05),其余差异均不具有统计学意义(P>0.05)。所有受试者均无鹅口疮及声音嘶哑发生;两组用药前后血常规、肝功能、肾功能、心肌酶、心电图均无明显差异(P>0.05)。结论雾化FP(0.5 mg)治疗2~4岁哮喘患儿急性发作期的疗效与雾化BUD(1 mg)相比无显著性差异,安全性良好;雾化FP在治疗第2天的夜间哮喘症状控制优于雾化BUD;在轻度哮喘发作患儿中,雾化FP在治疗第2、4天夜间哮喘症状控制优于雾化BUD。

Objective To observe the efficacy and safety of fluticasone propionate nebuliser suspension(FP nebuliser)in the treatment of acute asthma attack in children aged 2~4 years.Methods A randomized,active drug controlled,multicenter clinical study design was adopted.Totally 245 children aged 2 to 4 years old with acute asthma in 10 hospitals from June 2022 to February 2023 were randomly divided into FP nebulizer group and Budesonide suspension for inhalation(BUD nebuliser)group according to the ratio of 1.5:1.Observe the daily daytime and nighttime clinical symptom scores,respiratory index scores,and differences from baseline in two groups,as well as the use of other asthma relief drugs to evaluate effectiveness.Use the difference between the daytime clinical symptom scores and baseline on the third day as the main efficacy indicator,and further conduct subgroup analysis based on the severity of asthma.Evaluate safety by observing changes in blood and biochemical indicators(routine blood,liver function,myocardial enzyme,kidney function electrocardiogram)before and after medication,as well as the incidence of adverse events.Finally 239 cases completed the 5~7-day study.Results There was no statistically significant difference in the main efficacy indicators between the two groups(P>0.05).The difference between clinical symptoms and baseline on the second day at night in the FP nebuliser group was higher than that in the BUD nebuliser group(P<0.05).The clinical symptom scores of FP nebuliser group on the 4th day were higher than those of BUD nebuliser group(P<0.05).At other time points,there was no statistically significant difference between the two groups in daytime symptom scores,nighttime clinical symptom scores,respiratory index scores,or differences trom baseline(P>0.05).There was no statistically significant difference in the number and frequency of concurrent use of systemic glucocorticoids between the FP nebuliser group and the BUD nebuliser group(P>0.05).In children with mild asthma attacks,the difference between the nighttime clinical symptom scores and baseline in the FP nebuliser group on the 2nd and 4th day was greater than that in the BUD nebuliser group(P<0.05),and there was no significant difference in the other differences.All subjects had no oral candidiasis or hoarse voice.There was no significant difference in routine blood,liver and kidney function,myocardial enzymes,or electrocardiogram between the two groups before and after medication(P>0.05).Conclusion FP nebuliser suspension(0.5 mg)has no difference in efficacy compared to BUD suspension(1 mg)in the asthma at acute attack period in 2~4-year old children,and has good safety.FP nebuliser is superior to BUD nebuliser in controlling nocturnal asthma symptoms on the 2nd day of treatment;FP nebuliser is superior to BUD nebuliser in controlling nocturnal asthma symptoms on the 2nd and 4th day of mild asthma attacks.