Olav L Schjørring1,2,3, Thomas L Klitgaard1,2, Anders Perner3,4,5, Jørn Wetterslev3,6, Theis Lange3,7, Frederik Keus8, Jon H Laake9, Matthew Morgan10,11, Minna Bäcklund12, Martin Siegemund13, Katrin M Thormar14, Bodil S Rasmussen1,2,3. 1. Department of Anaesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark. 2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 3. Centre for Research in Intensive Care (CRIC), Copenhagen, Denmark. 4. Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Denmark. 5. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 6. Department 7812, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Denmark. 7. Department of Biostatistics, Copenhagen University, Copenhagen, Denmark. 8. Department of Critical Care, University Medical Centre of Groningen, University of Groningen, Groningen, the Netherlands. 9. Division of Emergencies and Critical Care, Rikshospitalet, Oslo University Hospital, Oslo, Norway. 10. Critical Care Research, University Hospital of Wales, Cardiff, UK. 11. Cardiff University School of Medicine, Wales, UK. 12. Department of Perioperative, Intensive Care and Pain Medicine, Helsinki University Hospital, Helsinki, Finland. 13. Department of Intensive Care and Department of Clinical Research, University Hospital, University of Basel, Basel, Switzerland. 14. Department of Anaesthesia and Intensive Care, Landspitali, University Hospital, Reykjavik, Iceland.
Abstract
BACKGROUND: No solid evidence exists on optimal oxygenation targets in intensive care patients. The handling oxygenation targets in the intensive care unit (HOT-ICU) trial assesses the effects of a targeted arterial oxygen tension of 8 vs 12 kPa on 90-day mortality in acutely admitted adult patients with hypoxaemic respiratory failure. This article describes the detailed statistical analysis plan for the predefined outcomes and supplementary analyses in the HOT-ICU trial. METHODS: The trial will include 2928 patients to be able to detect or reject a true 20% relative risk reduction in the primary outcome of 90-day all-cause mortality with an α of 5% and a β of 10%. Analyses of the primary and secondary outcomes will be conducted according to the intention-to-treat principle and adjusted for stratification variables. The primary outcome and dichotomous secondary outcomes will be analysed using a generalised linear model with a log-link and binomial error distribution. For the primary outcome, a 95% confidence interval (CI) not including 1.00 for the risk ratio will be considered statistically significant. Continuous secondary outcomes will be analysed using a generalised linear model or nonparametric test. CIs adjusted for the multiple secondary outcomes not including the null effect will be considered statistically significant. One planned interim analysis has been conducted. CONCLUSIONS: The HOT-ICU trial and the pre-planned statistical analyses are designed to minimise bias and produce high quality data on the effects of a lower vs a higher oxygenation target throughout ICU admission in acutely admitted adult patients with hypoxaemic respiratory failure. REGISTRATION: ClinicalTrials.gov identifier: NCT03174002, date of registration: June 2, 2017. European clinical trials database, EudraCT number 2017-000632-34.
BACKGROUND: No solid evidence exists on optimal oxygenation targets in intensive care patients. The handling oxygenation targets in the intensive care unit (HOT-ICU) trial assesses the effects of a targeted arterial oxygen tension of 8 vs 12 kPa on 90-day mortality in acutely admitted adult patients with hypoxaemic respiratory failure. This article describes the detailed statistical analysis plan for the predefined outcomes and supplementary analyses in the HOT-ICU trial. METHODS: The trial will include 2928 patients to be able to detect or reject a true 20% relative risk reduction in the primary outcome of 90-day all-cause mortality with an α of 5% and a β of 10%. Analyses of the primary and secondary outcomes will be conducted according to the intention-to-treat principle and adjusted for stratification variables. The primary outcome and dichotomous secondary outcomes will be analysed using a generalised linear model with a log-link and binomial error distribution. For the primary outcome, a 95% confidence interval (CI) not including 1.00 for the risk ratio will be considered statistically significant. Continuous secondary outcomes will be analysed using a generalised linear model or nonparametric test. CIs adjusted for the multiple secondary outcomes not including the null effect will be considered statistically significant. One planned interim analysis has been conducted. CONCLUSIONS: The HOT-ICU trial and the pre-planned statistical analyses are designed to minimise bias and produce high quality data on the effects of a lower vs a higher oxygenation target throughout ICU admission in acutely admitted adult patients with hypoxaemic respiratory failure. REGISTRATION: ClinicalTrials.gov identifier: NCT03174002, date of registration: June 2, 2017. European clinical trials database, EudraCT number 2017-000632-34.
Authors: Elena Crescioli; Thomas Lass Klitgaard; Lone Musaeus Poulsen; Bjørn Anders Brand; Martin Siegemund; Thorbjørn Grøfte; Frederik Keus; Ulf Gøttrup Pedersen; Minna Bäcklund; Johanna Karttunen; Matthew Morgan; Andrei Ciubotariu; Anne-Marie Gellert Bunzel; Stine Rom Vestergaard; Nicolaj Munch Jensen; Thomas Steen Jensen; Maj-Brit Nørregaard Kjær; Aksel Karl Georg Jensen; Theis Lange; Jørn Wetterslev; Anders Perner; Olav Lilleholt Schjørring; Bodil Steen Rasmussen Journal: Intensive Care Med Date: 2022-04-20 Impact factor: 41.787
Authors: Thomas L Klitgaard; Olav L Schjørring; Theis Lange; Morten H Møller; Anders Perner; Bodil S Rasmussen; Anders Granholm Journal: Br J Anaesth Date: 2021-10-19 Impact factor: 9.166
Authors: Bodil S Rasmussen; Thomas L Klitgaard; Anders Perner; Björn A Brand; Thomas Hildebrandt; Martin Siegemund; Alexa Hollinger; Søren R Aagaard; Morten H Bestle; Klaus V Marcussen; Anne C Brøchner; Christoffer G Sølling; Lone M Poulsen; Jon H Laake; Tayyba N Aslam; Minna Bäcklund; Marjatta Okkonen; Matthew Morgan; Mike Sharman; Theis Lange; Jørn Wetterslev; Olav L Schjørring Journal: Acta Anaesthesiol Scand Date: 2021-09-20 Impact factor: 2.274
Authors: Frederik Mølgaard Nielsen; Thomas Lass Klitgaard; Elena Crescioli; Søren Rosborg Aagaard; Anne Sofie Andreasen; Lone Musaeus Poulsen; Martin Siegemund; Anne Craveiro Brøchner; Morten H Bestle; Susanne Andi Iversen; Björn A Brand; Jon Henrik Laake; Thorbjørn Grøfte; Thomas Hildebrandt; Theis Lange; Anders Perner; Olav Lilleholt Schjørring; Bodil Steen Rasmussen Journal: Acta Anaesthesiol Scand Date: 2021-08-12 Impact factor: 2.274