Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial
Anthony C Gordon, Alexina J Mason, Neeraja Thirunavukkarasu, Gavin D Perkins, Maurizio Cecconi, Magda Cepkova, David G Pogson, Hollmann D Aya, Aisha Anjum, Gregory J Frazier, Shalini Santhakumaran, Deborah Ashby, Stephen J Brett, VANISH Investigators, Deborah Ashby, Jane Warwick, Sandra Griffiths, Mary Cross, Neeraja Thirunavukkarasu, Aisha Anjum, Alexina Mason, Gregory Frazier, Shalinin Santhakumaran, Nayan Das, Geoff Bellingan, Anthony Gordon, Stephen Brett, Gavin Perkins, Deborah Ashby, Richard Beale, Frances Banks, Terence Watts, Peter Andrews, Daniel McAuley, Timothy Collier, Maie Templeton, Emily Errington, Kirsty Gladas, Anthony Gordon, Dorota Banach, David Kitson, Rosemary Matthew-Thomas, Stephen Brett, Verena Hauer, Adaeze Ochelli-Okpue, Martin Stotz, Marlies Ostermann, Katie Lei, Kathryn Chan, John Smith, Manu Shankar-Hari, Jamie Carungcong, Jonathan Handy, Phil Hopkins, Clair-Louise Harris, Fiona Wade-Smith, Sian Birch, Tom Hurst, Johannes Mellinghoff, Nora Di Tomasso, Claudia Ebm, Fabrizio Iannuccelli, Maurizio Cecconi, Christopher J Kirwan, Thais Creary, Carmen Correia, John R Prowle, Nicola Jaques, Abby Brown, Andrew Walden, Jozef Joscak, Josephine Bangalan, Tiina Tamm, Lisa Snow, Clare Stapleton, Sheik M Y Pahary, Magda Cepkova, Tim Gould, Jeremy Bewley, Katie Sweet, Lisa Grimmer, Sanjoy Shah, Sarah Williams, Mark Pulletz, Kim Golder, Clare Bolger, Karen Salmon, Benjamin Skinner, Emma Vickers, Michelle Scott, Steve Rose, Nikki Lamb, Johanna Mouland, David Pogson, Lynne Bullock, Martin Bland, Donna Harrison-Briggs, Kate Wilkinson, Anton Krige, Geraldine Ward, Jeffrey Ting, Christopher Bassford, Anthony C Gordon, Alexina J Mason, Neeraja Thirunavukkarasu, Gavin D Perkins, Maurizio Cecconi, Magda Cepkova, David G Pogson, Hollmann D Aya, Aisha Anjum, Gregory J Frazier, Shalini Santhakumaran, Deborah Ashby, Stephen J Brett, VANISH Investigators, Deborah Ashby, Jane Warwick, Sandra Griffiths, Mary Cross, Neeraja Thirunavukkarasu, Aisha Anjum, Alexina Mason, Gregory Frazier, Shalinin Santhakumaran, Nayan Das, Geoff Bellingan, Anthony Gordon, Stephen Brett, Gavin Perkins, Deborah Ashby, Richard Beale, Frances Banks, Terence Watts, Peter Andrews, Daniel McAuley, Timothy Collier, Maie Templeton, Emily Errington, Kirsty Gladas, Anthony Gordon, Dorota Banach, David Kitson, Rosemary Matthew-Thomas, Stephen Brett, Verena Hauer, Adaeze Ochelli-Okpue, Martin Stotz, Marlies Ostermann, Katie Lei, Kathryn Chan, John Smith, Manu Shankar-Hari, Jamie Carungcong, Jonathan Handy, Phil Hopkins, Clair-Louise Harris, Fiona Wade-Smith, Sian Birch, Tom Hurst, Johannes Mellinghoff, Nora Di Tomasso, Claudia Ebm, Fabrizio Iannuccelli, Maurizio Cecconi, Christopher J Kirwan, Thais Creary, Carmen Correia, John R Prowle, Nicola Jaques, Abby Brown, Andrew Walden, Jozef Joscak, Josephine Bangalan, Tiina Tamm, Lisa Snow, Clare Stapleton, Sheik M Y Pahary, Magda Cepkova, Tim Gould, Jeremy Bewley, Katie Sweet, Lisa Grimmer, Sanjoy Shah, Sarah Williams, Mark Pulletz, Kim Golder, Clare Bolger, Karen Salmon, Benjamin Skinner, Emma Vickers, Michelle Scott, Steve Rose, Nikki Lamb, Johanna Mouland, David Pogson, Lynne Bullock, Martin Bland, Donna Harrison-Briggs, Kate Wilkinson, Anton Krige, Geraldine Ward, Jeffrey Ting, Christopher Bassford
Abstract
Importance: Norepinephrine is currently recommended as the first-line vasopressor in septic shock; however, early vasopressin use has been proposed as an alternative.
Objective: To compare the effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock.
Design, setting, and participants: A factorial (2×2), double-blind, randomized clinical trial conducted in 18 general adult intensive care units in the United Kingdom between February 2013 and May 2015, enrolling adult patients who had septic shock requiring vasopressors despite fluid resuscitation within a maximum of 6 hours after the onset of shock.
Interventions: Patients were randomly allocated to vasopressin (titrated up to 0.06 U/min) and hydrocortisone (n = 101), vasopressin and placebo (n = 104), norepinephrine and hydrocortisone (n = 101), or norepinephrine and placebo (n = 103).
Main outcomes and measures: The primary outcome was kidney failure-free days during the 28-day period after randomization, measured as (1) the proportion of patients who never developed kidney failure and (2) median number of days alive and free of kidney failure for patients who did not survive, who experienced kidney failure, or both. Rates of renal replacement therapy, mortality, and serious adverse events were secondary outcomes.
Results: A total of 409 patients (median age, 66 years; men, 58.2%) were included in the study, with a median time to study drug administration of 3.5 hours after diagnosis of shock. The number of survivors who never developed kidney failure was 94 of 165 patients (57.0%) in the vasopressin group and 93 of 157 patients (59.2%) in the norepinephrine group (difference, -2.3% [95% CI, -13.0% to 8.5%]). The median number of kidney failure-free days for patients who did not survive, who experienced kidney failure, or both was 9 days (interquartile range [IQR], 1 to -24) in the vasopressin group and 13 days (IQR, 1 to -25) in the norepinephrine group (difference, -4 days [95% CI, -11 to 5]). There was less use of renal replacement therapy in the vasopressin group than in the norepinephrine group (25.4% for vasopressin vs 35.3% for norepinephrine; difference, -9.9% [95% CI, -19.3% to -0.6%]). There was no significant difference in mortality rates between groups. In total, 22 of 205 patients (10.7%) had a serious adverse event in the vasopressin group vs 17 of 204 patients (8.3%) in the norepinephrine group (difference, 2.5% [95% CI, -3.3% to 8.2%]).
Conclusions and relevance: Among adults with septic shock, the early use of vasopressin compared with norepinephrine did not improve the number of kidney failure-free days. Although these findings do not support the use of vasopressin to replace norepinephrine as initial treatment in this situation, the confidence interval included a potential clinically important benefit for vasopressin, and larger trials may be warranted to assess this further.
Trial registration: clinicaltrials.gov Identifier: ISRCTN 20769191.
Source: PubMed