Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial
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Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin’s effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock.
In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20–160 µg/h with maximum infusion rate of 4 mg/day) or NE (4–30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population.
Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55–1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: − 7 (IQR − 11 to 3) in the terlipressin group and − 6 (IQR − 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001).
In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events.
This trial is registered at ClinicalTrials.gov: ID NCT01697410.
KeywordsTerlipressin Norepinephrine Septic shock SOFA score
We would like to thank all of the doctors, nurses, technicians and patients involved at the participating centres for their dedication to the study. We also thank Xuyu Zhang, Michael Quintel, Ström Christer, JL Teboul, Jianfeng Wu and Yao Nie for their kind help with the manuscript. This study was funded by Sun Yat-sen University Clinical Research Program 5010 (NO 2007015) and by Major Science and Technology Project (NO 2012A080204018) of Guangdong province, China.
Study Group of investigators
Xiang-Dong Guan, Zi-Meng Liu and Juan Chen (The First Affiliated Hospital of Sun Yatsen University); Aihua Lin, Jie Zeng and Yanlin Huang (School of Public Health, Sun Yat-sen University), Qiuye Kou and Enhe Liu (The Sixth Affiliated Hospital of Sun Yatsen University), Qinhan Lin and Jianling Liu (Qingyuan People's Hospital), Xiaobo Huang and Xiaoqin Zhang (Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital), Zhanhong Tang and Yaoping Pan (The First Affiliated Hospital, GuangXi Medical University), Yan Kang and Yao Chen (West China Hospital), Ke Li and Jiji Cheng (Chinese PLA 302 Hospital), Lixin Zhou and Xinhua Qiang (Foshan First Municipal People’s Hospital), Qing Song and Li Wang (Chinese PLA General Hospital), Tongwen Sun (The First Affiliated Hospital, Zhengzhou University), Ling Zhao and Jiwen Zhong (Zhuhai People's Hospital), Xue Wang and Hongli Chen (The First Affiliated Hospital, Xi,An JiaoTong University), Xiandi He and Qiang Wu (The First Affiliated Hospital, Bengbu Medical college), Chunting Wang and Juan Zeng(Shandong Provincial Hospital), Benquan Wu and Jinmei Luo (The Third Affiliated Hospital of Sun Yat-sen University), Jiandong Lin and Zhaohui Fu (Fujian Provincial Hospital), Shiying Yuan(Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology), Qin Gu and Ning Liu (The Affiliated Drum Tower hospital of Nanjing University Medical school), Kejian Qian (The First Affiliated Hospital, Nanchang University), Xianqing Shi(Guizhou Provincial Hospital), Yongwen Feng and Suiqing Gui (The Second People's Hospital of Shenzhen).
ZL and JC contributed eaqually to this work. ZL, JC and XG designed the research; QK, JC, QL, XH, ZT, YK, KL, LZ, QS, TS, LZ, XW, XH, CW, BW, JL, SY, QG, KQ, XS and YW performed the research and collected data; AL analysed the data; ZL wrote the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflicts of interest
We declare no competing interests.
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