多中心、随机、开放性评价磷酸奥司他韦颗粒剂治疗儿童流感疑似病例的有效性及安全性

Efficacy and safety of oseltamivir in children with suspected influenza： a multicenter randomized open-label trial

目的研究磷酸奥司他韦颗粒剂治疗儿童流感疑似病例的有效性及安全性。方法采用多中心、随机、开放性研究。收集广东省5所医院（广州市妇女儿童医疗中心、深圳市宝安区妇幼保健院、汕头大学医学院第二附属医院、东莞市妇幼保健院、广州市越秀区儿童医院）2015年4月至7月门诊收治的儿童流感疑似病例229例，随机分为2组。对照组115例，给予愈酚伪麻口服溶液作为基础治疗，连续给药5d；试验组114例，给予基础治疗加上磷酸奥司他韦颗粒剂，同样连续给药5d。观察磷酸奥司他韦颗粒剂疗效和安全性。结果（1）治疗前两组疑似病例在病情严重程度上差异无统计学意义。治疗后试验组比对照组，在疾病持续时间（h）[69．9（95％C165．3～91．5）比75．4（95％C169．9-91．7）]、发热持续时间（h）[40．4（95％CI31．5-53．4）比44．0（95％CI33．2～50．0）]上差异虽无统计学意义，但均有所缩短。（2）229例中有73例（31．9％）流感病毒检测阳性，治疗后试验组（42例）比对照组（31例），疾病持续时间缩短约55h，流感症状持续时间缩短近60h；两组差异有统计学意义（P〈0．05）。发热持续时间（h）[32．8（95％CI24．0～47．0）比55．8（95％CI43．7-78．3）]虽缩短23h，但差异无统计学意义（P〉0．05）。（3）73例流感病毒检测阳性病例中完成治疗方案的患儿共60例，试验组（38例）比对照组（22例）发热持续时间（h）[34．8（95％CI24．0-48．5）比53．3（95％C143．6～104．0）]缩短近19h，差异有统计学意义（P〈0．05）。（4）不良反应发生率：试验组（10％）比对照组（2％），差异有统计学意义（P〈0．05），不良反应多为消化道症状，多可自行缓解。结论2015年4至7月广东省5所医院门诊收治的儿童流感疑似病例流感病毒阳性率31．9％；疑似病例中，予磷酸奥司他韦颗粒剂治疗的与未予磷酸奥司他韦颗粒剂治疗的，在疾病持续时间、发热持续时间虽统计学未达显著界值，但数值上均较其缩短；流感病毒阳性病例中，予磷酸奥司他韦颗粒剂治疗的比未予磷酸奥司他韦颗粒剂治疗的，疾病持续时间明显缩短；完成用药疗程更有利于缓解发热。且不良反应小，应用安全。

Objective To evaluate the efficacy and safety of oseltamivir in the treatment of suspected influenza in children. Method A multicenter, randomized and open-label trial was conducted among 229 individuals with suspected influenza which were collected from the clinic of 5 hospitals in Guangdong province （Guangzhou Women and Children＇s Medical Center, Shenzhen Baoan District Maternity and Child Care Service Center, the Second Affiliated Hospital of Shantou University Medical College, Dongguan Maternity and Child Care Service Centre, Yuexiu District Children＇s Hospital of Guangzhou） from April to July 2015. They were randomized either to oseltamivir group （oseltamivir 30 -75 mg, twice daily for 5 days） or control group who were given symptom relief medicines for 5 days. Result No significant difference was found between two groups in influenza symptoms of the patients before the treatment （P 〉 0. 05）. Altogether 229 individuals （114 in osehamivir group, 115 in control group） were analyzed for efficacy, in which 73 individuals （42 oseltamivir, 31 control）, 31.9%, were identified as influenza- infected through laboratory test. No significant difference was found between the two groups in the duration of fever although shortened. In the 229 individuals , the cumulative alleviation proportion between oseltamivir and control group was not significantly different （P 〉 0. 05 ） ： the median duration of illness was 69. 9 hours （95 % C1 65.3 - 91.5 ） in osehamivir group and 75.4 hours （95% CI 63.9 - 91. 7 ） in control group ; the median duration of fever was 40.4 hours （95% CI 31.5 - 53.4） in oseltamivir group and 44. 0 hours （95% CI 33.2- 50. 0） in control group. In the 73 individuals, the cumulative alleviation proportion between osehamivir and control group was significantly different （ P 〈 0. 05 ）. The median duration of illness was 61.2 hours （95% CI 48.0 - 121. 0） in oseltamivir group, being significantly shorter than that of 116. 0 hours （95% C191.5 -175.0） in control group. But it was not significantly different that the median duration of fever was 32. 8 hours （ 95% CI 24.0 - 47.0 ） in osehamivir group and 55. 8 hours （95% CI 43.6 - 78.3 ） in control group （P 〉0. 05）. And the median duration of fever in 60 individuals （38 oseltamivir, 22 control） was significantly different between two groups（P 〈0.05 ） , who had finished a course of taking osehamivir in the 73 individuals, 34. 8 hours （95 % CI 24. 0 - 48.5 ） in osehamivir group being significantly shorter than that of 53.3 hours （95% CI 43.6 - 104. 0 ） in control group. There was certain difference in side effects rate between the two groups （ osehamivir 10% , control 2% , P 〈 0. 05 ）. The main side-effects were gastrointestinal symptoms （ stomachache, diarrhea, poor appetite, vomiting ） . Conclusion The duration of illness and fever in suspected influenza patients treated with oseltamivir was shorter than those in the patients treated with no oseltamivir, the difference was not statistically significant, when 31.9% was confirmed with positive result of virus test in suspected influenza in children. But in these patients with positive result of virus test, the duration of illness was significantly shortened with treatment with oseltamivir as compared with no treatment with oseltamivir, and it would be better if full oseltamivir course was completed for reducing the duration of fever. Oseltamivir treatment was safe with mild side effects.