补肾生血法与益气养血法联合西药治疗再生障碍性贫血的前瞻性随机双盲安慰剂对照的多中心临床研究

Treatment of Aplastic Anemia with the Method of Kidney Nourishing and Blood Engendering and the Method of Qi Boosting and Blood Nourishing Combined with Western Medicine:A Prospective,Randomized,Double-blind,Placebo-controlled,Multi-center Clinical Stu

目的比较补肾生血法、益气养血法联合基础西药治疗再生障碍性贫血的临床有效性及安全性。方法采用前瞻、随机、双盲、安慰剂对照、多中心研究方法。以分层区组随机法将患者分为补肾生血组、益气养血组、对照组,中药治疗分别予补肾填精颗粒、补益气血颗粒、安慰剂(半量补肾填精颗粒),均联合口服环孢素A及雄激素。3个月为1个疗程,连续观察两个疗程治疗前后的血常规[包括白细胞计数(WBC)、血红蛋白含量(HGB)、血小板计数(PLT)、中性粒细胞计数(ANC)]、输血情况、中医证候积分、生活质量评分、安全性指标,并记录不良事件,治疗结束后1年进行随访并评定疗效。结果共纳入585例,剔除18例,进入FAS总病例数567例,其中补肾生血组184例、益气养血组191例和对照组192例,因失访共脱落75例。补肾生血组总有效率(86.4%)明显优于益气养血组(78.0%)与对照组(72.9%,P<0.001)。各组治疗后HGB、PLT、WBC均升高(P<0.05),尤以补肾生血组最佳(P<0.05);补肾生血组治疗后及随访时HGB明显高于益气养血组与对照组(P<0.05),治疗后益气养血组HGB高于对照组(P<0.05);补肾生血组随访时PLT明显高于其余两组(P<0.001);各组治疗后及随访时WBC均升高(P<0.05)。各组治疗后ANC均下降(P<0.05),但补肾生血组与益气养血组随访时ANC均有回升(P<0.001),而对照组ANC持续下降(P<0.001)。各组输血情况均有改善(P<0.05),其中补肾生血组患者输血人数最早清零(P<0.05);各组中医证候总积分均降低,生活质量评分均提高(P<0.05)。观察期间均未出现与治疗相关的严重不良事件。结论补肾生血法、益气养血法联合西药治疗再生障碍性贫血疗效确切,安全性良好,可有效降低中医证候评分并提高生活质量评分,其中补肾生血法疗效更佳。

ObjectiveTo explore and compare the clinical effect and safety of kidney nourishing and blood engendering method(KNBE),and qi boosting and blood nourishing method(QBBN)in addition to basic western medicine in the treatment of aplastic anemia.MethodsA prospective,double-blind,randomized placebo-controlled,multicenter study was designed.With a randomized block method,the patients were divided into KNBE group,QBBN group and control group,accepting Bushen Tianjing Granules(补肾填精颗粒),Buyi Qixue Granules(补益气血颗粒)and placebo(half amount ofBushen Tianjing Granules),respectively,in addition to oral cyclosporine A and androgen.All groups were treated for two courses,with 3 months as a course.The blood routine test indicators including white blood cell count(WBC),hemoglobin content(HGB),platelet count(PLT)and neutrophil count(ANC),the blood transfusion,traditional Chinese medicine(TCM)syndrome score,quality of life score,and safety indicators were evaluated before and after treatment,and the adverse events were recorded.Follow-up was performed 1 year after treatment and the effect was assessed.ResultsOf the initially included 585 cases,18 cases were excluded,and 567 cases were analyzed in the full analysis set(FAS)including 184 cases in the KNBE group,191 cases in the QBBN group and 192 cases in the control group.A total of 75 cases dropped out due to loss to follow-up.The total effective rate of the KNBE group was 86.4%,significantly higher than 78.0%of the QBBN group and 79.2%of the control group(P<0.001).After treatment,the levels of HGB,PLT and WBC in the three groups all increased(P<0.05),and the KNBE group was the highest(P<0.05).The HGB level in the KNBE group was significantly higher than that of QBBN group and control group after treatment and at follow up(P<0.05),and that in the QBBN group was higher than in the control group(P<0.05).The PLT level in the KNBE group was significantly higher than that of the other groups at follow up(P<0.001).The WBC levels in the three groups significantly increased after treatment and at follow up(P<0.05).The ANC level decreased in all three groups after treatment(P<0.001),but at follow up,it increased in KNBE and QBBN group while continuously decreased in the control group(P<0.001).The blood transfusion conditions of all the three groups improved(P<0.05),and the number of participants in need of blood transfusions in the KNBE group was the first to be reduced to zero(P<0.05).The total TCM syndrome score decreased in all three groups,while the scores of quality of life increased(P<0.05).No serious adverse events related to treatment occurred during the observation period.ConclusionThe combination of KNBE and QBBN with western medicine has definite curative effect and sound safety in treating aplastic anemia,and can effectively reduce TCM syndrome score and improve the quality of life.Moreover,KNBE group has better effect.