M Krag1, A Perner1,2, J Wetterslev2,3, T Lange4,5, M P Wise6, M Borthwick7, S Bendel8, P Pelosi9, F Keus10, A B Guttormsen11, J C Schefold12, T S Meyhoff1, S Marker1, M H Møller1. 1. Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 2. Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 3. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 4. Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 5. Center for Statistical Science, Peking University, Beijing, China. 6. Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK. 7. Pharmacy Department, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 8. Department of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland. 9. Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino IST, University of Genoa, Genoa, Italy. 10. Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 11. Department of Anaesthesia and Intensive Care, Haukeland University Hospital and Clinical Institute 1 UiB, Bergen, Norway. 12. Department of Intensive Care Medicine, Inselspital, Bern University Hospital, Bern, Switzerland.
Abstract
BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.
RCT Entities:
BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficileinfection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION:Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.
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: Søren Marker; Anders Perner; Jørn Wetterslev; Mette Krag; Theis Lange; Matt P Wise; Mark Borthwick; Stepani Bendel; Frederik Keus; Anne Berit Guttormsen; Joerg C Schefold; Morten Hylander Møller Journal: Intensive Care Med Date: 2019-03-12 Impact factor: 17.440
Authors: M W Munch; Anders Granholm; S N Myatra; Bkt Vijayaraghavan; Maria Cronhjort; R R Wahlin; Stephan M Jakob; Luca Cioccari; M N Kjaer; G K Vesterlund; T S Meyhoff; Marie Helleberg; M H Møller; Thomas Benfield; Balasubramanian Venkatesh; Naomi Hammond; Sharon Micallef; Abhinav Bassi; Oommen John; Vivekanand Jha; K T Kristiansen; C S Ulrik; V L Jørgensen; Margit Smitt; Morten H Bestle; A S Andreasen; L M Poulsen; B S Rasmussen; A C Brøchner; Thomas Strøm; Anders Møller; M S Khan; Ajay Padmanaban; J V Divatia; Sanjith Saseedharan; Kapil Borawake; Farhad Kapadia; Subhal Dixit; Rajesh Chawla; Urvi Shukla; Pravin Amin; Michelle S Chew; Christian Gluud; Theis Lange; Anders Perner Journal: Acta Anaesthesiol Scand Date: 2021-03-09 Impact factor: 2.274
Authors: Ingrid Toews; Aneesh Thomas George; John V Peter; Richard Kirubakaran; Luís Eduardo S Fontes; Jabez Paul Barnabas Ezekiel; Joerg J Meerpohl Journal: Cochrane Database Syst Rev Date: 2018-06-04
Authors: Marie Warrer Petersen; Tine Sylvest Meyhoff; Marie Helleberg; Maj-Brit Nørregaard Kjaer; Anders Granholm; Carl Johan Steensen Hjortsø; Thomas Steen Jensen; Morten Hylander Møller; Peter Buhl Hjortrup; Mik Wetterslev; Gitte Kingo Vesterlund; Lene Russell; Vibeke Lind Jørgensen; Klaus Tjelle; Thomas Benfield; Charlotte Suppli Ulrik; Anne Sofie Andreasen; Thomas Mohr; Morten H Bestle; Lone Musaeus Poulsen; Mette Friberg Hitz; Thomas Hildebrandt; Lene Surland Knudsen; Anders Møller; Christoffer Grant Sølling; Anne Craveiro Brøchner; Bodil Steen Rasmussen; Henrik Nielsen; Steffen Christensen; Thomas Strøm; Maria Cronhjort; Rebecka Rubenson Wahlin; Stephan Jakob; Luca Cioccari; Balasubramanian Venkatesh; Naomi Hammond; Vivekanand Jha; Sheila Nainan Myatra; Christian Gluud; Theis Lange; Anders Perner Journal: Acta Anaesthesiol Scand Date: 2020-07-30 Impact factor: 2.274