探索中成药治疗儿童咳嗽变异性哮喘的有效性与安全性——小儿咳喘颗粒Ⅱ期临床试验方案设计

Efficacy and safety of treatment with Chinese patent medicine on children's cough variant asthma——Protocol of phase Ⅱ clinical trials by Xiao'er Kechuan Granule

目的初步评价中成药治疗儿童咳嗽变异性哮喘的有效性与安全性,为治疗咳嗽变异性哮喘的中药研发与疾病的临床研究提供参考。方法采用区组随机、双盲双模拟、剂量探索、阳性药平行对照、多中心临床试验的方法,将144例患儿以1∶1∶1∶1的比例分到高、低剂量,安慰剂以及阳性药组,口服小儿咳喘颗粒试验药及模拟剂,孟鲁司特钠片及其模拟剂。疗程均为4周。以咳嗽严重程度的日平均分为主要疗效指标;把疾病控制情况评估,活动受限、夜间症状、缓解药/急诊需求情况,呼气峰值流速(PEF)日变异率,以及中医证候疗效作为次要疗效指标;以不良事件作为主要安全性指标。结果建立咳嗽变异性哮喘的评价体系,制定纳入、排除、脱落标准以及主、次要评价指标,并规范了入组时不同慢性咳嗽的鉴别诊断要求。结论通过小儿咳喘颗粒Ⅱ期临床试验方案设计,对中成药治疗儿童咳嗽变异性哮喘的有效性与安全性进行了有益的探索,在目前条件下该方案具有可操作性。

Objective To evaluate the effectiveness and safety of Chinese patent medicine(CPM) in the treatment of children’s cough variant asthma(CVA), and to provide an example for the clinical study design of CVA. Methods Using block randomized, double-blind, double-dummy, dose exploration, parallel, active-controlled, and multi-center clinical research method, 144 cases of children with CVA were divided into high dose group, low dose group, placebo group, and positive drug group(1:1:1:1). Children are treated with Xiao’er Kechuan Granule, Montelukast, and their placebos for 4 weeks. The average score of cough severity(day and night) was used as the main evaluation index. Assessment of disease control, limited activity, nocturnal symptom, situation of rescue medication/emergency requirement, PEF mutation rate per day, and efficacy of TCM syndrome were detected as secondary indexes. Incidence of adverse events/reaction was used as the main security evaluation index. Results The phase II clinical trials of Xiao’er Kechuan Granule are designed, the effectivity and safety of CPM in the treatment of CVA are explored, and the method has maneuverability under the existing conditions.