清解宣透肺卫方银花平感颗粒治疗上呼吸道感染邪郁肺卫证的安全性和有效性研究：一项随机双盲、阳性药物平行对照、多中心临床试验

A safety and effectiveness research of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription for treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase： a randomized double blinded, positive drug parallel controlled and multicentric clinical trial

目的 评价清解宣透肺卫方银花平感颗粒治疗上呼吸道感染邪郁肺卫证的安全性及有效性,探索最佳有效剂量.方法 采用随机双盲、阳性药平行对照、多中心临床试验方法,收集浙江中医药大学附属第一医院、江西中医药大学附属医院、天津中医药大学第二附属医院、浙江省立同德医院、福建省中医药研究院收治的270例感冒患者,最终符合方案集（PPS）人群242例纳入研究,其中高剂量组观察82例,低剂量组观察79例,对照组81例.高、低剂量观察组分别按每日3次、每次1袋和每日2次、每次1袋的方法给予银花平感颗粒（每袋5 g）;对照组给予银翘解毒颗粒（每袋5 g）每次1袋、每日3次;两组均连续口服1个疗程（3 d）后评价疗效.主要疗效评价指标包括上呼吸道感染中医证候总评分、主症总评分;次要疗效评价指标包括主症发热恶寒不同评分患者情况及发热恶寒症状消失情况;并观察临床综合疗效及中性粒细胞比例变化,评价其用药安全性.结果 在PPS人群中,对照组及高、低剂量观察组治疗后中医证候总评分（分）和主症总评分（分）均较治疗前明显降低,3 d时出现统计学差异（分别为4.4±3.9比15.5±4.6、3.7±3.2比15.0±4.3、3.0±2.7比15.2±3.9,2.8±2.6比9.7±2.7、2.3±2.1比9.5±2.5、2.0±1.9比9.6±2.4,均P〈0.01）.对照组及高、低剂量观察组治疗1 d后主症发热恶寒评分为6分的患者数均较治疗前明显减少（分别为7比32例、6比31例、4比28例）,治疗3 d后主症发热恶寒评分为0的患者数均较治疗前明显增加（65、73、77例比0例）,评分为3分的患者数均较治疗前明显减少（分别为16比47例、5比46例、5比52例）,对照组和高剂量观察组无评分为6分的患者,仅低剂量观察组出现1例评分为6分的患者,表明高、低剂量观察组和对照组均可缓解临床症状;且评分为0和3分患者数的变化以高、低剂量观察组较对照组更加明显（分别为73、77比65例,5、5比16例,均P〈0.05）,表明银花平感颗粒组解热作用优于银翘解毒颗粒.高、低剂量观察组发热恶寒症状消失率明显高于对照组〔93.9%（77/82）、92.4%（73/79）比80.2%（65/81）,均P〈0.05〕.高、低剂量观察组中医证候疗效愈显率和有效率均高于对照组〔分别为87.80%（72/82）、79.75%（63/79）比74.07%（60/81）和98.78%（81/82）、96.20%（76/79）比96.30%（78/81）〕;高、低剂量观察组上呼吸道感染症状疗效愈显率和有效率也均高于对照组〔分别为78.05%（64/82）、74.68%（59/79）比65.43%（78/81）和98.78%（81/82）、96.20%（76/79）比96.30%（78/81）〕,3组间疗效比较具有临床实际意义,但差异均无统计学意义（均P〉0.05）.高、低剂量观察组和对照组治疗后中性粒细胞比例均较治疗前明显降低（分别为0.61±0.08比0.63±0.08、0.62±0.08比0.64±0.08、0.61±0.09比0.64±0.09,均P〈0.05）.银花平感颗粒在方案规定的疗程、治疗剂量范围内安全性良好.结论 银花平感颗粒是治疗上呼吸道感染邪郁肺卫证安全有效的药物.

Objective To evaluate the safety and efficacy of Yinhua Pinggan granule of Qingjie Xuantou lung defense prescription in the treatment of patients with upper respiratory tract infection accompanied by traditional Chinese medicine （TCM） syndrome of pathogen stagnated in lung-defense phase and to explore the best effective dose.Methods A randomized double blinded, positive drug parallel controlled and multicentric clinical trial was conducted, 270 patients with upper respiratory infection were collected from the First Affiliated Hospital of Zhejiang Chinese Medical University, Affiliated Hospital of Jiangxi Medical University, the Second Affiliated Hospital of Tianjin University of TCM, Tongde Hospital of Zhejiang Province, and Fujian Province Institute of TCM, after screening only 242 cases were consistent with the criteria of enrollment into the Per-Protocol Set （PPS） population, and they were divided into three groups： high dose observation group （82 cases）, low dose observation group （79 cases） and control group （81 cases）. The high and low dose observation groups were treated with Yinhua Pinggan granule （5 g per bag）, high dose means once 1 bag orally taken 3 times a day, low dose indicates once 1 bag taken twice a day; the control group was treated with Yinqiao Jiedu granule （5 g per bag） once 1 bag, 3 times a day; the curative effects of the above groups were all evaluated after consecutive oral administration of the drug respectively for 1 therapeutic course （3 days）. The main efficacy evaluation indexes included the TCM syndrome total score and the total score of main symptoms of upper respiratory tract infection; the secondary efficacy evaluation indexes included the situations of patients with different scores of main symptoms of fever and chills, and of disappearance of TCM symptoms; the clinical comprehensive therapeutic effect and the changes of proportion of neutrophils were observed and the safety of drugs was evaluated.Results In PPS population, after treatment the TCM syndrome total score and the total score of main symptoms in the control group and the high and low dose observation groups were all significantly lower than those before treatment, on the 3rd day statistical significant differences were shown （4.4±3.9 vs. 15.5±4.6, 3.7±3.2 vs. 15.0±4.3, 3.0±2.7 vs. 15.2±3.9, 2.8±2.6 vs. 9.7±2.7, 2.3±2.1 vs. 9.5±2.5, 2.0±1.9 vs. 9.6±2.4, respectively, all P 〈 0.01）. After treatment for 1 day, the numbers of patients with 6 score in the control group and the high and low dose observation groups were reduced significantly compared with those before treatment in main symptoms of fever with chills （7 vs. 32 cases, 6 vs. 31 cases, 4 vs. 28 cases, respectively）; 3 days after treatment, compared with those before treatment, the numbers of patients with main symptoms of fever with chills score being 0 were significantly increased in the above three groups （65, 73, 77 cases vs. 0 cases, respectively）, the numbers of patients with the score being 3 were significantly decreased （16 vs. 47 cases, 5 vs. 46 cases, 5 vs. 52 cases, respectively）; the control and high dose observation group had no patients with the score being 6, there was only 1 case with the score being 6 in the low dose observation group. The results showed that the treatments of high and low dose observation groups and the control group all could alleviate the clinical symptoms, and the changes of numbers of patients with the scoresbeing 0 and 3 in high and low dose groups were more significant than those in the control group （respectively 73, 77 vs. 65 cases, 5, 5 vs. 16 cases, allP 〈 0.05）, showing that the antipyretic effect of Yinhua Pinggan granule was superior to that of the Yinqiao Jiedu granule. The disappearance rates of fever with chills symptoms in high and low dose observation groups were significantly higher than that in the control group [respectively 93.9% （77/82）, 92.4% （73/79） vs. 80.2% （65/81）, allP 〈 0.05]. The TCM syndrome cure and obvious effect rate and effective rate in high and low dose observation groups were higher than those in the control group [respectively 87.80% （72/82）, 79.75% （63/79） vs. 74.07% （60/81） and 98.78% （81/82）, 96.20% （76/79） vs. 96.30% （78/81）]; the cure and marked effective rate and effective rate of controlling symptoms of upper respiratory tract infection in high and low dose observation groups were higher than those in the control group [respectively 78.05% （64/82）, 74.68% （59/79） vs. 65.43% （78/81） and 98.78% （81/82）, 96.20% （76/79） vs. 96.30% （78/81）], comparisons of efficacy among the three groups possessed clinical practical significance, but the differences were not statistically significant （allP 〉 0.05）. The percentages of neutrophils in high and low dose observation groups and control group were significantly lower than those before treatment （respectively 0.61±0.08 vs. 0.63±0.08, 0.62±0.08 vs. 0.64±0.08, 0.61±0.09 vs. 0.64±0.09, allP 〈 0.05）. Yinhua Pinggan granule was safe in the prescribed course of treatment and range of therapeutic dose.Conclusions Yinhua Pinggan granule is a safe and effective drug in the treatment of patients with upper respiratory tract infection accompanied by syndrome of pathogen stagnated in lung-defense phase.