Søren Marker1,2, Anders Perner3,4, Jørn Wetterslev4,5, Mette Krag3,4, Theis Lange6,7, Matt P Wise8, Mark Borthwick9, Stepani Bendel10, Frederik Keus11, Anne Berit Guttormsen12,13, Joerg C Schefold14, Morten Hylander Møller3,4. 1. Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. soeren.marker@regionh.dk. 2. Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. soeren.marker@regionh.dk. 3. Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. 4. Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 5. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 6. Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 7. Center for Statistical Science, Peking University, Beijing, China. 8. Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK. 9. Pharmacy Department, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 10. Department of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland. 11. Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 12. Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway. 13. Department of Clinical Medicine, UiB, Bergen, Norway. 14. Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Abstract
PURPOSE: In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further. METHODS: The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53. RESULTS: A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00-1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96-1.22 and 1.10; 95% CI 0.97-1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes. CONCLUSIONS: In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. CLINICALTRIALS.GOV: ClinicalTrials.gov No. NCT02467621.
RCT Entities:
PURPOSE: In the subgroup of patients with Simplified Acute Physiology Score (SAPS) II > 53 in the Stress Ulcer Prophylaxis in Intensive Care Unit (SUP-ICU) trial, there was interaction (P = 0.049) suggesting increased mortality in patients allocated to pantoprazole as compared with placebo. We aimed to explore this further. METHODS: The SUP-ICU trial allocated acutely admitted adults at risk of gastrointestinal bleeding to pantoprazole vs placebo. In this post hoc study, we repeated all the preplanned analyses of SUP-ICU in patients with baseline SAPS II > 53. RESULTS: A total of 1140 patients had a complete SAPS II > 53 and were included. At 90 days, 272/579 patients (47%) assigned to pantoprazole had died, as compared with 229/558 patients (41%) assigned to placebo [relative risk 1.13; 95% confidence interval (CI) 1.00-1.29]. This was supported by sensitivity analyses adjusted for risk factors and those in the per-protocol population. When accounting for patients with incomplete SAPS II in two additional analyses, the relative risk was 1.08; 95% CI 0.96-1.22 and 1.10; 95% CI 0.97-1.25. This was also observed for the secondary outcome days alive without life support. There were no differences between the intervention groups in the other secondary outcomes. CONCLUSIONS: In this post hoc analysis of patients with high disease severity included in the SUP-ICU trial, we observed higher 90-day mortality and fewer days alive without life support with pantoprazole vs placebo. Some of this may have been explained by missing SAPS II data, but further research is needed to draw firm conclusions. CLINICALTRIALS.GOV: ClinicalTrials.gov No. NCT02467621.
Authors: Shane P Selvanderan; Matthew J Summers; Mark E Finnis; Mark P Plummer; Yasmine Ali Abdelhamid; Michael B Anderson; Marianne J Chapman; Christopher K Rayner; Adam M Deane Journal: Crit Care Med Date: 2016-10 Impact factor: 7.598
Authors: Lars B Holst; Nicolai Haase; Jørn Wetterslev; Jan Wernerman; Anne B Guttormsen; Sari Karlsson; Pär I Johansson; Anders Aneman; Marianne L Vang; Robert Winding; Lars Nebrich; Helle L Nibro; Bodil S Rasmussen; Johnny R M Lauridsen; Jane S Nielsen; Anders Oldner; Ville Pettilä; Maria B Cronhjort; Lasse H Andersen; Ulf G Pedersen; Nanna Reiter; Jørgen Wiis; Jonathan O White; Lene Russell; Klaus J Thornberg; Peter B Hjortrup; Rasmus G Müller; Morten H Møller; Morten Steensen; Inga Tjäder; Kristina Kilsand; Suzanne Odeberg-Wernerman; Brit Sjøbø; Helle Bundgaard; Maria A Thyø; David Lodahl; Rikke Mærkedahl; Carsten Albeck; Dorte Illum; Mary Kruse; Per Winkel; Anders Perner Journal: N Engl J Med Date: 2014-10-01 Impact factor: 91.245
Authors: Andrew Rhodes; Laura E Evans; Waleed Alhazzani; Mitchell M Levy; Massimo Antonelli; Ricard Ferrer; Anand Kumar; Jonathan E Sevransky; Charles L Sprung; Mark E Nunnally; Bram Rochwerg; Gordon D Rubenfeld; Derek C Angus; Djillali Annane; Richard J Beale; Geoffrey J Bellinghan; Gordon R Bernard; Jean-Daniel Chiche; Craig Coopersmith; Daniel P De Backer; Craig J French; Seitaro Fujishima; Herwig Gerlach; Jorge Luis Hidalgo; Steven M Hollenberg; Alan E Jones; Dilip R Karnad; Ruth M Kleinpell; Younsuk Koh; Thiago Costa Lisboa; Flavia R Machado; John J Marini; John C Marshall; John E Mazuski; Lauralyn A McIntyre; Anthony S McLean; Sangeeta Mehta; Rui P Moreno; John Myburgh; Paolo Navalesi; Osamu Nishida; Tiffany M Osborn; Anders Perner; Colleen M Plunkett; Marco Ranieri; Christa A Schorr; Maureen A Seckel; Christopher W Seymour; Lisa Shieh; Khalid A Shukri; Steven Q Simpson; Mervyn Singer; B Taylor Thompson; Sean R Townsend; Thomas Van der Poll; Jean-Louis Vincent; W Joost Wiersinga; Janice L Zimmerman; R Phillip Dellinger Journal: Intensive Care Med Date: 2017-01-18 Impact factor: 17.440
Authors: Mette Krag; Anders Perner; Jørn Wetterslev; Matt P Wise; Mark Borthwick; Stepani Bendel; Colin McArthur; Deborah Cook; Niklas Nielsen; Paolo Pelosi; Frederik Keus; Anne Berit Guttormsen; Alma D Moller; Morten Hylander Møller Journal: Intensive Care Med Date: 2015-04-10 Impact factor: 17.440
Authors: Mette Krag; Søren Marker; Anders Perner; Jørn Wetterslev; Matt P Wise; Joerg C Schefold; Frederik Keus; Anne B Guttormsen; Stepani Bendel; Mark Borthwick; Theis Lange; Bodil S Rasmussen; Martin Siegemund; Helle Bundgaard; Thomas Elkmann; Jacob V Jensen; Rune D Nielsen; Lisbeth Liboriussen; Morten H Bestle; Jeanie M Elkjær; Dorte F Palmqvist; Minna Bäcklund; Jon H Laake; Per M Bådstøløkken; Juha Grönlund; Olena Breum; Akil Walli; Robert Winding; Susanne Iversen; Inge-Lise Jarnvig; Jonathan O White; Björn Brand; Martin B Madsen; Lars Quist; Klaus J Thornberg; Anders Møller; Jørgen Wiis; Anders Granholm; Carl T Anthon; Tine S Meyhoff; Peter B Hjortrup; Søren R Aagaard; Jo B Andreasen; Christina A Sørensen; Pernille Haure; Jacob Hauge; Alexa Hollinger; Jonas Scheuzger; Daniel Tuchscherer; Thierry Vuilliomenet; Jukka Takala; Stephan M Jakob; Marianne L Vang; Kim B Pælestik; Karen L D Andersen; Iwan C C van der Horst; Willem Dieperink; Jesper Fjølner; Cilia K W Kjer; Christine Sølling; Christoffer G Sølling; Johanna Karttunen; Matt P G Morgan; Brit Sjøbø; Janus Engstrøm; Birgit Agerholm-Larsen; Morten H Møller Journal: N Engl J Med Date: 2018-10-24 Impact factor: 91.245
Authors: T S G Sehested; T A Gerds; E L Fosbøl; P W Hansen; M G Charlot; N Carlson; M A Hlatky; C Torp-Pedersen; G H Gislason Journal: J Intern Med Date: 2017-11-07 Impact factor: 8.989
Authors: Anders Granholm; Søren Marker; Mette Krag; Fernando G Zampieri; Hans-Christian Thorsen-Meyer; Benjamin Skov Kaas-Hansen; Iwan C C van der Horst; Theis Lange; Jørn Wetterslev; Anders Perner; Morten Hylander Møller Journal: Intensive Care Med Date: 2020-01-14 Impact factor: 17.440
Authors: Michael O Harhay; Jonathan D Casey; Marina Clement; Sean P Collins; Étienne Gayat; Michelle Ng Gong; Samir Jaber; Pierre-François Laterre; John C Marshall; Michael A Matthay; Rhonda E Monroe; Todd W Rice; Eileen Rubin; Wesley H Self; Alexandre Mebazaa Journal: Intensive Care Med Date: 2020-02-18 Impact factor: 17.440
Authors: Paul J Young; Sean M Bagshaw; Andrew B Forbes; Alistair D Nichol; Stephen E Wright; Michael Bailey; Rinaldo Bellomo; Richard Beasley; Kathy Brickell; Glenn M Eastwood; David J Gattas; Frank van Haren; Edward Litton; Diane M Mackle; Colin J McArthur; Shay P McGuinness; Paul R Mouncey; Leanlove Navarra; Dawn Opgenorth; David Pilcher; Manoj K Saxena; Steve A Webb; Daisy Wiley; Kathryn M Rowan Journal: JAMA Date: 2020-02-18 Impact factor: 56.272
Authors: Melanie Smith Condeni; Alyson T Basting; Patrick G Costello; Ashley DePriest; Evert A Eriksson; Heather Evans; Kristie Hertel; Andre L Holder; Alyssa N Kester; Kinsey R Kowalski; Carolyn Magee Bell; Barbara McLean; Michael Reichert; Melissa Santibañez; Patrick M Wieruszewski; Andrea Sikora Newsome Journal: J Crit Care Date: 2020-12-27 Impact factor: 3.425