摘要
目的 观察磷酸奥司他韦在自然获得流行性感冒 (以下简称流感 )受试者中的临床疗效、安全性及耐受性。方法 采用随机、双盲和安慰剂对照的多中心临床试验设计。共入组 478例 ,入组条件为年龄≥ 18岁 ,≤ 6 5岁 ;发热≥ 37 8℃ ;至少有两个流感样症状 ;出现症状后不超过 36h。合格的受试者随机接受磷酸奥司他韦 75mg或安慰剂治疗 ,每日 2次 ,共 5d。结果 证实为流感患者(即ITTI总体 )有 2 73例 ,试验组 134例 ,对照组 139例。ITTI总体试验组疾病持续时间中位数为 91 6h(95 %可信区间为 80 2~ 10 1 3h) ,对照组疾病持续时间中位数为 95 0h(95 %可信区间为 84 5~10 5 3h) ,两组疾病缓解率差异有显著性 (P =0 0 46 6 )。ITTI总体试验组症状总分下降值的曲线下面积中位数为 1382 9,明显高于对照组 (12 36 7,P =0 0 196 )。共有 45 9例可进行安全性分析 ,试验组和对照组不良反应发生率差异无显著性。不良反应主要为消化系统症状。结论 磷酸奥司他韦在流感发病后早期使用可以明显缩短疾病的持续时间、减轻症状的严重程度 ,其安全性和耐受性较好 ,适合在临床中推广使用。
Objective To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza in China. Methods A randomized,double-blinded, placebo controlled trial of oseltamivir was conducted in China. Individuals of 18 to 65 years were enrolled presenting within 36 hours of influenzal symptoms and elevated temperature of 37.8 or higher .They should have at least two of the following symptoms :nasal congestion, sore throat, cough, myalgia, fatigue, headache,chill and sweating) during an influenza outbreak in the community. Individuals were randomized either to oseltamivir group(75 mg twice daily for 5 days ) or placebo group. Results A total of 478 individuals were recruited, 16(3.35%) failed to follow up or refused to continue the trial, 3(0.6%) were excluded immediately before taking medication because they did not meet the entry criteria and 8(1.7%) individuals were excluded in the blinding review meeting because of protocol violation. Altogether 451 individuals were analyzed for efficacy as intent-to-treat population (ITT)(216 oseltamivir, 235 placebo) and 273 individuals were identified as influenza-infected through laboratory test;they were defined as intent-to-treat infected population (ITTI) (134 oseltamivir, 139 placebo). For safety analysis, 459 individuals were included. In ITTI population, the cumulative alleviation proportion in oseltamivir group was significantly higher than that of placebo group (P=0.046 6). The median duration of illness was 91.6 hours [95% confident interval (CI) 80.2~101.3 hours] in oseltamivir group and 95.0 hours (95% CI 84.5~105.3 hours) in placebo group. The median area under the curve(AUC) of decreased total score was significantly higher in oseltamivir group than in placebo group, being 1 382.9 and 1 236.7 score-hours respectively (P=0.019 6). The median duration of fever and myalgia were 27.9 and 35.5 hours in oseltamivir group, being significantly shorter than that of 51.5 and 36.0 hours in placebo group (P=0.000 1 and 0.036 1). The median AUC of decreased score for fever and nasal symptom was 337.9 and 108.5 in oseltamivir group, being significantly higher than that of 311.3 and 43.3 in placebo group (P=0.011 8 and 0.040 3). The proportion of subjects reporting fever in oseltamivir group were significantly lower than that in placebo group at 36, 60, 72, 96, 120 and 132 hours after the initiation of treatment (P=0.049, 0.001, 0.001, 0.007, 0.007 and 0.030). The amount of paracetamol taken, incidence of secondary complications and antibiotics usage associated with secondary complications were similar in the two groups (P=0.085 1, 0.944, 1.000). For ITT population, similar results were seen. Adverse events reported were similar in oseltamivir and placebo group. The main adverse events were gastrointestial symptoms, headache,vertigo, and rashes. Conclusion Oseltamivir was effective and well tolerated in the treatment of early naturally acquired influenza.
出处
《中华内科杂志》
CAS
CSCD
北大核心
2001年第12期838-842,共5页
Chinese Journal of Internal Medicine