国产卡泊芬净经验性治疗粒缺伴发热患者的疗效和安全性研究

中国真菌学杂志　 2021, Vol. 16 　Issue (5): 308-313.

国产卡泊芬净经验性治疗粒缺伴发热患者的疗效和安全性研究

杨小珠¹, 梁爱斌², 郑晓云¹, 傅建非², 侯明³, 孙爱宁⁴, 陆化⁵, 金洁⁶, 胡建达¹

1. 福建医科大学附属协和医院血液科, 福建省血液病研究所, 福建省血液病学重点实验室, 福州 350001;
2. 同济大学附属同济医院血液科, 上海 200065;
3. 山东大学齐鲁医院血液科, 济南 250012;
4. 苏州大学附属第一医院血液科, 苏州 215006;
5. 江苏省人民医院血液科, 苏州 210029;
6. 浙江大学医学院附属第一医院血液病科, 杭州 310003

收稿日期:2020-12-25 发布日期:2021-10-28
通讯作者: 胡建达,E-mail:drjiandahu@163.com E-mail:drjiandahu@163.com
作者简介:杨小珠,女(汉族),硕士,主治医师.E-mail:327148343@qq.com

The efficacy and safety of domestic caspofungin for empirical therapy in patients with agranulocytosis and fever

YANG Xiaozhu¹, LIANG Aibin², ZHENG Xiaoyun¹, FU Jianfei², HOU Ming³, SUN Aining⁴, LU Hua⁵, JIN Jie⁶, HU Jianda¹

1. Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fuzhou 350001, China;
2. Department of Hematology, Tongji Hospital, Tongji University, Shanghai 200065, China;
3. Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China;
4. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China;
5. Department of Hematology, Jiangsu Province Hospital, Nanjing 210029, China;
6. Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

Received:2020-12-25 Published:2021-10-28

摘要/Abstract

摘要： 目的对于中性粒细胞缺乏（粒缺）伴持续性发热住院患者，在前期对比国产与原研卡泊芬净经验性抗真菌治疗的药代动力学试验的基础上，进一步评价国产卡泊芬净的疗效和安全性。方法本研究为前瞻性、多中心、开放临床试验（ClinicalTrials.gov注册号NCT03857399）。纳入粒缺伴持续性发热住院患者，在卡泊芬净经验性治疗结束后，对全部患者进行国产卡泊芬净的疗效和安全性评估。结果共入组32例，纳入全分析集（FAS）32例，符合方案集（PPS）30例。FAS和PPS中，国产卡泊芬净的临床有效率分别为71.88%（23/32）和76.67%（23/30），疗程分别为（13.22±5.80） d和（13.70±5.62） d。治疗结束0~2 d内，退热率分别为78.13%（25/32）和80%（24/30）、中性粒细胞绝对值计数（ANC）>0.5×10⁹/L的占比分别为75%（24/32）和76.67%（23/30）。治疗结束后28 d内的生存率分别为81.25%（26/32）和83.33%（25/30）。国产卡泊芬净的耐受性较好，不良事件多为1~2级，大多与其无关，均未导致用药减少或停药，药物相关不良事件发生率3.1%（1/32），为1例肝功能异常。无药物相关的严重不良事件发生。结论国产卡泊芬净经验性治疗粒缺伴持续性发热患者获得了良好的临床疗效和安全性。

关键词: 中性粒细胞缺乏, 发热, 国产卡泊芬净, 临床有效率, 安全性

Abstract: Objective In the hospitalized patients with agranulocytosis and persistent fever, the efficacy and safety of domestic caspofungin were further evaluated on the basis of the previous study which comparing the pharmacokinetic characteristics of domestic and original caspofungin for empirical antifungal therapy. Methods This study was a prospective, multi-center, open clinical trial (ClinicalTrials.gov Identifier:NCT03857399). Hospitalized patients with agranulocytosis and persistent fever were enrolled. After the empirical treatment of caspofungin, the efficacy and safety of domestic caspofungin in all patients were evaluated. Results Of the 32 patients enrolled, there were 32 patients in full analysis set (FAS) and 30 patients in Per-protocol Set (PPS). In the FAS and PPS, the clinical efficacy rate of domestic caspofungin were 71.88%(23/32) and 76.67%(23/30), the treatment courses were (13.22±5.80) days and (13.70±5.62) days, respectively. Within 0 to 2 days after treatment, the pyretolysis rate were 78.13%(25/32) and 80%(24/30), and the proportion of patients whose absolute neutrophil count over 0.5×10⁹/L were 75%(24/32) and 76.67%(23/30) in the two set. The 28-day survival rate after treatment were 81.25%(26/32) and 83.33%(25/30), respectively. Domestic caspofungin was well tolerated. Most of the adverse events were grade 1 to grade 2 and drug-unrelated, no adverse events led to dosage decreased or withdrew. The incidence of drug-related adverse events was 3.1%(1/32), including 1 case of hepatic dysfunction. No drug-related serious adverse events occurred. Conclusions Domestic caspofungin had achieved great clinical efficacy and safety as empirical antifungal therapy in patients with agranulocytosis and persistent fever.

Key words: agranulocytosis, fever, domestic caspofungin, clinical efficacy rate, safety

中图分类号:

R978.5

杨小珠, 梁爱斌, 郑晓云, 傅建非, 侯明, 孙爱宁, 陆化, 金洁, 胡建达. 国产卡泊芬净经验性治疗粒缺伴发热患者的疗效和安全性研究[J]. 中国真菌学杂志, 2021, 16(5): 308-313.

YANG Xiaozhu, LIANG Aibin, ZHENG Xiaoyun, FU Jianfei, HOU Ming, SUN Aining, LU Hua, JIN Jie, HU Jianda. The efficacy and safety of domestic caspofungin for empirical therapy in patients with agranulocytosis and fever[J]. Chinese Journal of Mycology, 2021, 16(5): 308-313.

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