Han Mei, Lai Lily, Li Xin-Xue, Zhao Nan-Qi, Li Jing, Xia Yun, Liu Jian-Ping
School of Traditional medicine, Beijing University of Chinese Medicine, China.
Primary Care and Population Sciences, University of Southampton, UK.
Evid Based Complement Alternat Med. 2019 Apr 11;2019:6486293. doi: 10.1155/2019/6486293. eCollection 2019.
To summarize the characteristics and the outcomes of the Randomized Placebo-Controlled Trials of Chinese Herbal Medicine Granules manufactured by China Resources Sanjiu Pharmaceutical Co., Ltd.
Databases including China National Knowledge Infrastructure, VIP, Wanfang, PubMed, Cochrane Library, and clinicaltrials.gov were searched in March 2018 for relevant randomized controlled trials (RCTs). Two reviewers independently screened for and selected studies, extracted data, and checked data extraction. Methodological quality was evaluated using the Cochrane Risk of Bias tool. For the outcome, the characteristics of the study, the cure rate, the effectiveness rate, and advert events were described with a method of bibliometrics. Also, we performed meta-analysis only if there were ≥2 studies treated by the same intervention and evaluated by the same outcome.
A total of 40 placebo-controlled RCTs treated for 17 diseases were included in our analysis involving 4,632 patients. 16 of 19 studies treated by CHM granules only showed positive result in patients with HBV, HCV, fever, depression, nonalcoholic fatty liver disease, AIDS, and asthma while negative result was shown in patients with migraine. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in patients with HBV, herpes simplex keratitis, COPD, liver cirrhotic ascites, Parkinson's disease, and diabetic peripheral neuropathy while negative result was shown in patients with myasthenia gravis, angina pectoris, and depression. The pooled result cannot demonstrate that the notifying kidney formula granules had the superior effect with placebo on the clearance of serum HBV DNA and HBeAg in HBV carriers with a RR (and the 95% CI) of 2.97 [0.74,11.91] and 1.99 [0.93,4.29], respectively. But, the CHM granules can reduce within-group HBV DNA levels by more than 2 lgIU/ml; the RR (and 95% CI) was 4.64 [2.89,7.45]. Qizhu granules had a significant effect on clearance of HCV RNA with a RR (and 95% CI) of 6.26 [2.16,18.16]. And, the heat-clearing and detoxifying formula granules were superior to placebo in resolution of cold symptom among patients with fever with a RR and 95% CI of 2.58 [1.40,4.74]. Based on the conventional therapy, the pooled result demonstrated that the Regulating liver formula granules were superior to placebo on the clearance of serum HBeAg in chronic hepatitis B patients with a RR (and the 95% CI) of 1.73 [1.30,2.31]. The EeChen decoction granules were superior to placebo in COPD patients with a RR (and the 95% CI) of 1.13 [1.06,1.22]. 28 of the 40 studies reported adverse events. There were 51 adverse events in CHM formula granules group or combination group (n=2,483) and 26 in control group (n=2,122) totally. Most of the adverse symptoms spontaneously resolved after completing the courses of treatment and the other adverse symptoms improved after symptomatic treatment.
16 of 19 studies treated by CHM granules only showed positive result in 7 diseases and negative result in 1 disease. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in 6 diseases and negative result in 3 diseases. However, both the absolute and relative effectiveness of CHM formula granules compared with placebo need to be considered clinically.
总结华润三九医药股份有限公司生产的中药配方颗粒随机安慰剂对照试验的特征及结果。
于2018年3月检索中国知网、维普、万方、PubMed、Cochrane图书馆和clinicaltrials.gov等数据库，查找相关随机对照试验（RCT）。两名研究者独立筛选并选择研究、提取数据及核对数据提取情况。采用Cochrane偏倚风险工具评估方法学质量。对于结果，采用文献计量学方法描述研究特征、治愈率、有效率及不良事件。此外，仅当有≥2项研究采用相同干预措施且以相同结局进行评估时，才进行荟萃分析。
我们的分析共纳入40项针对17种疾病的安慰剂对照RCT，涉及4632例患者。19项仅采用中药配方颗粒治疗的研究中，16项在乙肝、丙肝、发热、抑郁、非酒精性脂肪性肝病、艾滋病和哮喘患者中显示出阳性结果，而在偏头痛患者中显示出阴性结果。21项联合疗法与传统疗法对比的研究中，17项在乙肝、单纯疱疹性角膜炎、慢性阻塞性肺疾病（COPD）、肝硬化腹水、帕金森病和糖尿病周围神经病变患者中显示出阳性结果，而在重症肌无力、心绞痛和抑郁患者中显示出阴性结果。汇总结果无法证明通知肾方颗粒在乙肝携带者血清乙肝病毒脱氧核糖核酸（HBV DNA）和乙肝e抗原（HBeAg）清除方面比安慰剂具有更优效果，其相对危险度（RR）（及95%可信区间）分别为2.97 [0.74, 11.91] 和1.99 [0.93, 4.29]。但是，中药配方颗粒可使组内HBV DNA水平降低超过2 logIU/ml；RR（及95%可信区间）为4.64 [2.89, 7.45]。芪术颗粒在丙肝病毒核糖核酸（HCV RNA）清除方面具有显著效果，RR（及95%可信区间）为6.26 [2.16, 18.16]。并且，清热解毒配方颗粒在发热患者感冒症状缓解方面优于安慰剂，RR及95%可信区间为2.58 [1.40, 4.74]。基于传统疗法，汇总结果表明，调肝配方颗粒在慢性乙肝患者血清HBeAg清除方面优于安慰剂，RR（及95%可信区间）为1.73 [, 2.31]。莪陈汤颗粒在COPD患者中优于安慰剂，RR（及95%可信区间）为1.13 [1.06, 1.22]。40项研究中有28项报告了不良事件。中药配方颗粒组或联合组（n = 2483）共有51例不良事件，对照组（n = 2122）共有26例。大多数不良症状在完成疗程后自行缓解，其他不良症状经对症治疗后改善。
19项仅采用中药配方颗粒治疗的研究中，16项在7种疾病中显示出阳性结果而在1种疾病中显示出阴性结果。21项联合疗法与传统疗法对比的研究中，17项在6种疾病中显示出阳性结果而在3种疾病中显示出阴性结果。然而，中药配方颗粒与安慰剂相比的绝对及相对有效性在临床中均需予以考虑。
