PMID- 34510762 OWN - NLM STAT- MEDLINE DCOM- 20220325 LR - 20220325 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 27 IP - 12 DP - 2021 Dec TI - Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study). PG - 1493-1503 LID - 10.1111/cns.13724 [doi] AB - AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population. CI - (c) 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. FAU - Ni, Jun AU - Ni J AUID- ORCID: 0000-0002-7877-612X AD - Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Yao, Ming AU - Yao M AD - Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Wang, Li-Hua AU - Wang LH AD - Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Yu, Ming AU - Yu M AD - Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Li, Run-Hui AU - Li RH AD - Department of Neurology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China. FAU - Zhao, Li-Hong AU - Zhao LH AD - Department of Neurology, Dandong People's Hospital, Dandong, China. FAU - Wang, Jia-Chun AU - Wang JC AD - Department of Neurology, No. 1 Hospital of Harbin, Harbin, China. FAU - Wang, Yin-Zhou AU - Wang YZ AD - Department of Neurology, Fujian Provincial Hospital, Fuzhou, China. FAU - Wang, Xin AU - Wang X AD - Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Song, Hai-Qing AU - Song HQ AD - Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China. FAU - Luo, Ben-Yan AU - Luo BY AUID- ORCID: 0000-0002-9892-5778 AD - Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. FAU - Wang, Jia-Wei AU - Wang JW AD - Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Huang, Yi-Ning AU - Huang YN AD - Department of Neurology, Peking University First Hospital, Beijing, China. FAU - Cui, Li-Ying AU - Cui LY AD - Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. CN - RESK Investigators LA - eng PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210912 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - EC 3.4.21.- (Kallikreins) SB - IM MH - Aged MH - Female MH - Humans MH - Ischemic Stroke/*drug therapy MH - Kallikreins/administration & dosage/adverse effects/*pharmacology MH - Male MH - Middle Aged MH - Outcome Assessment, Health Care PMC - PMC8611767 OTO - NOTNLM OT - acute ischemic stroke OT - clinical trial OT - efficacy OT - human urinary kallidinogenase OT - safety COIS- All authors report no conflicts. FIR - Cui, Li-Ying IR - Cui LY FIR - Ni, Jun IR - Ni J FIR - Yao, Ming IR - Yao M FIR - Li, Run-Hui IR - Li RH FIR - Zhao, Li-Hong IR - Zhao LH FIR - Wang, Li-Hua IR - Wang LH FIR - Wang, Jia-Chun IR - Wang JC FIR - Yu, Ming IR - Yu M FIR - Hao, Yan-Lei IR - Hao YL FIR - Liu, Xin-Ping IR - Liu XP FIR - Lin, Jie IR - Lin J FIR - Shi, Bao-Lin IR - Shi BL FIR - Li, Long-Xuan IR - Li LX FIR - Li, Shi-Ze IR - Li SZ FIR - Zhang, Chao-Dong IR - Zhang CD FIR - Wei, Xiu-E IR - Wei XE FIR - Wei, Ya-Fen IR - Wei YF FIR - Li, Guang-Hua IR - Li GH FIR - Luo, Ben-Yan IR - Luo BY FIR - Zhang, Jian-Jun IR - Zhang JJ FIR - Wang, Li-Yun IR - Wang LY FIR - Zhou, Ying-Qi IR - Zhou YQ FIR - Li, Xin-Yi IR - Li XY FIR - Li, Gao-Hua IR - Li GH FIR - Chen, Jun IR - Chen J FIR - Wang, Yin-Zhou IR - Wang YZ FIR - Wei, Yan IR - Wei Y FIR - Chen, Ji-Hua IR - Chen JH FIR - Liu, Wei-Min IR - Liu WM FIR - Bai, Qing-Ke IR - Bai QK FIR - Niu, Jian-Ping IR - Niu JP FIR - Kuang, Shi-Xiang IR - Kuang SX FIR - Dong, Mei IR - Dong M FIR - Li, Shi-Ping IR - Li SP FIR - Liu, Xin-Tong IR - Liu XT FIR - Gao, Xiang IR - Gao X FIR - Li, Yan-Song IR - Li YS FIR - Wang, Kai IR - Wang K FIR - Xiao, Wei-Min IR - Xiao WM FIR - Song, Hai-Qing IR - Song HQ FIR - Zhao, Guo-Hua IR - Zhao GH FIR - Hu, Xing-Yue IR - Hu XY FIR - Chen, Guo-Fang IR - Chen GF FIR - Li, Bo IR - Li B FIR - Ouyang, Kan IR - Ouyang K FIR - Wang, Xin IR - Wang X FIR - Shi, Fu-Ming IR - Shi FM FIR - Zhao, Yu-Wu IR - Zhao YW FIR - Li, Xiao-Gang IR - Li XG FIR - Wu, Dan-Hong IR - Wu DH FIR - Li, Qiang IR - Li Q FIR - Zhang, Jing-Bo IR - Zhang JB FIR - Yao, Guo-En IR - Yao GE FIR - Qin, Ding IR - Qin D FIR - Li, Gang IR - Li G FIR - Lu, Zheng-Qi IR - Lu ZQ FIR - Hou, Qian IR - Hou Q FIR - Huang, Guang IR - Huang G FIR - Lin, Xiao-Juan IR - Lin XJ FIR - Huang, Yi-Ning IR - Huang YN FIR - Peng, Jun IR - Peng J FIR - Qi, Xiao-Kun IR - Qi XK FIR - Wang, Jia-Wei IR - Wang JW FIR - Chen, Qi-Dong IR - Chen QD FIR - Ma, Qiang IR - Ma Q FIR - Xu, Ping-Yi IR - Xu PY FIR - Wang, Jia-Wei IR - Wang JW FIR - Luo, Shu-Yun IR - Luo SY EDAT- 2021/09/13 06:00 MHDA- 2022/03/26 06:00 PMCR- 2021/09/12 CRDT- 2021/09/12 21:36 PHST- 2021/08/13 00:00 [revised] PHST- 2021/07/26 00:00 [received] PHST- 2021/08/17 00:00 [accepted] PHST- 2021/09/13 06:00 [pubmed] PHST- 2022/03/26 06:00 [medline] PHST- 2021/09/12 21:36 [entrez] PHST- 2021/09/12 00:00 [pmc-release] AID - CNS13724 [pii] AID - 10.1111/cns.13724 [doi] PST - ppublish SO - CNS Neurosci Ther. 2021 Dec;27(12):1493-1503. doi: 10.1111/cns.13724. Epub 2021 Sep 12.