咖啡酸片治疗免疫性血小板减少症有效性和安全性 随机 双盲 平行对照多中心临床研究

A randomized, double-blind multicentre clinical trial comparing the efficacy and safety of Caffeic acid for the treatment of immune thrombocytopenia in China

目的评价咖啡酸片(CA)治疗免疫性血小板减少症(ITP)的有效性和安全性。方法 ITP入选的样本量来自2016年4—8月8个研究中心120例患者,随机分为观察组和对照组,每组各60例。观察组口服CA片(0.1 g/片)0.3 g/次,每日3次。对照组口服CA模拟片3片/次,每日3次。连服4周。观察两组;(1)安全指标:包括生命体征、血常规、肝功肾功、心电图和不良事件(AE)发生率。(2)疗效指标:(1)主要疗效指标:血小板数、血小板输注量、血小板恢复反应时间、有效率[完全反应(CR)率+有效(R)率]。(2)次要疗效指标,使用Kaplan-Meier法描述血小板恢复至≥80×10~9/L、≥100×10~9/L及提高血小板计数绝对值≥50×10~9/L所需时间。数据管理采用EP13.0。两组AE发生率比较采用Fisher确切概率法检验,并列表描述本次试验所发生的AE及实验室检验结果在试验前后正常或异常的变化情况。结果观察组与对照组有效率分别为41.82%对14.8%[全分析数据集(FAS)]和44.00%对15.38%[方案数据分析(PPS)](P=0.001)。两组血小板疗效有效率差的95%置信区间(CI)FAS为27%(10.89%~43.12%),PPS为28%(11.72%~45.51%)。两组均无输注血小板。观察组和对照组血小板恢复反应中位时间分别为17.00 d对34.00 d(FAS)及15.00 d对34.00 d(PPS)。两组有效率比较差异有统计学意义(P<0.05)。观察组未见明显的不良反应。结论 CA对ITP有较好的疗效,不良反应发生率较低且轻微,安全性可靠。

Objective To evaluate the effectiveness and safety of Caffeic acid tablets （CA） in the treatment of immune thrombocytopenia （ITP）. Method 120 patients with ITP were randomly divided into two groups： trial group and control group with 60 patients in each group. Trial group A receives（0.3 g CA 3 times daily） and Control group B receives（phcebo 3 times daily for 4 weeks. Safetyindicators： （ 1 ） Vital signs, blood routine tests, liver ＆ kidney function assays, electrocardiogram （ECG） and the incidence of adverse events （AE）. （2） Therapeutic indexes： （1） Major response effects： the platelet count, platelet transfusion amount, phtelet recovery reaction time, effectiveness （complete response rate （CR） ＋ response rate （R）） were compared between two groups. （ 2 ） Minor response effects： to use Kaplan Meier method was used to describe process of phtelet count recovery to up to 80 × 10 9/L, and 100 × 10 9/L, and platelet count increase time needed for reaching to absolute value 50 × 10 9/L or higher （per day） in two groups. （ 3 ） Data analysis： EP 13.0 was used. For comparison of incidence of adverse events between two groups, Fisher＇s exact probability method was used. AE and lab tests before and after study were also listed. Results Comparison beween group A and group B shows, the major response effects （CR ＋ R） were 41.82% and 14.81% （FAS） or 44.00% and 15.35% （PPS）; P = 0.001. There was significant difference in phtelet response with 95% confidence interval （95% CI） is 27% [ 10.89%-43.12%] （FAS）, or 28% [ 11.72%-45.51%] （PPS）. Both group A and group B had no phtelet transfusion. Platelet recovery reaction time （median time） in group A and group B were 17.00 and 34.00 （FAS） or 15.00 and 34.00 （PPS）. Comparison between two groups of patients shows, the CR rate ＋ R rate had statistically significant difference （P〈0.05）. Group A had no obvious adverse event. Condusion In ITP CA resulted in good response effect, low adverse events rate and reliable safety.