Zhenbin Ding1, Hong Wu2, Yongyi Zeng3, Ming Kuang4, Wei Yang5, Zhiqiang Meng6, Yajin Chen7, Chunyi Hao8, Shubing Zou9, Huichuan Sun1, Chang Liu2, Kecan Lin3, Guoming Shi1, Xiaoying Wang1, Xiutao Fu1, Rongxin Chen10, Yi Chen10, Ruifang Liang11, Takeshi Kano12, Huiyan Pan12, Suna Yang11, Jia Fan1,13, Jian Zhou14,15. 1. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. 2. Department of Liver Surgery and Liver Transplantation, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China. 3. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, Fujian, China. 4. Department of Liver Surgery, The First Affiliated Hospital of Sun Yat Sen University, Guangzhou, 510080, Guangdong, China. 5. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China. 6. Minimally Invasive Therapy Center, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. 7. Department of Hepatobiliary Surgery, Sun Yat Sen Memorial Hospital of Sun Yat Sen University, Guangzhou, 510120, Guangdong, China. 8. Department of Hepatobiliary Surgery, Beijing Cancer Hospital, Beijing, 100142, China. 9. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. 10. Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, 200032, China. 11. Eddingpharm Co, Ltd, Unit 122-129, Building A3, No. 700, Wanrong Road, Shanghai, China. 12. Shionogi & Co, Ltd, 3-13, Imabashi 3-chome, Chuou-ku, Osaka, 541-0042, Japan. 13. Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032, China. 14. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. zhou.jian@zs-hospital.sh.cn. 15. Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032, China. zhou.jian@zs-hospital.sh.cn.
Abstract
PURPOSE: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.
PURPOSE: Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 109/L) patients undergoing elective invasive procedures. METHODS: In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 109/L that increased to ≥ 20 × 109/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS: The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 109/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.
Authors: Douglas T Dieterich; David Bernstein; Steven Flamm; Paul J Pockros; Nancy Reau Journal: Aliment Pharmacol Ther Date: 2020-08-19 Impact factor: 8.171