TY - JOUR
T1 - Terlipressin versus norepinephrine as infusion in patients with septic shock
T2 - a multicentre, randomised, double-blinded trial
AU - Study Group Of Investigators
AU - Liu, Zi Meng
AU - Chen, Juan
AU - Kou, Qiuye
AU - Lin, Qinhan
AU - Huang, Xiaobo
AU - Tang, Zhanhong
AU - Kang, Yan
AU - Li, Ke
AU - Zhou, Lixin
AU - Song, Qing
AU - Sun, Tongwen
AU - Zhao, Ling
AU - Wang, Xue
AU - He, Xiandi
AU - Wang, Chunting
AU - Wu, Benquan
AU - Lin, Jiandong
AU - Yuan, Shiying
AU - Gu, Qin
AU - Qian, Kejian
AU - Shi, Xianqing
AU - Feng, Yongwen
AU - Lin, Aihua
AU - He, Xiaoshun
AU - Guan, Xiang Dong
AU - Zeng, Jie
AU - Huang, Yanlin
AU - Liu, Enhe
AU - Liu, Jianling
AU - Zhang, Xiaoqin
AU - Pan, Yaoping
AU - Chen, Yao
AU - Cheng, Jiji
AU - Qiang, Xinhua
AU - Wang, Li
AU - Zhong, Jiwen
AU - Chen, Hongli
AU - Wu, Qiang
AU - Zeng, Juan
AU - Luo, Jinmei
AU - Fu, Zhaohui
AU - Liu, Ning
AU - Gui, Suiqing
AU - Guan, Xiang Dong
N1 - Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature and ESICM.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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. Trial registration: This trial is registered at ClinicalTrials.gov: ID NCT01697410.
AB - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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. Trial registration: This trial is registered at ClinicalTrials.gov: ID NCT01697410.
KW - Norepinephrine
KW - SOFA score
KW - Septic shock
KW - Terlipressin
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U2 - 10.1007/s00134-018-5267-9
DO - 10.1007/s00134-018-5267-9
M3 - Article
C2 - 29971593
AN - SCOPUS:85049591851
SN - 0342-4642
VL - 44
SP - 1816
EP - 1825
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 11
ER -