TY - JOUR

T1 - Handling oxygenation targets in ICU patients with COVID-19—Protocol and statistical analysis plan in the HOT-COVID trial

AU - Mølgaard Nielsen, Frederik

AU - Lass Klitgaard, Thomas

AU - Crescioli, Elena

AU - Rosborg Aagaard, Søren

AU - Andreasen, Anne Sofie

AU - Musaeus Poulsen, Lone

AU - Siegemund, Martin

AU - Craveiro Brøchner, Anne

AU - Bestle, Morten H.

AU - Andi Iversen, Susanne

AU - Brand, Björn A.

AU - Laake, Jon Henrik

AU - Grøfte, Thorbjørn

AU - Hildebrandt, Thomas

AU - Lange, Theis

AU - Perner, Anders

AU - Lilleholt Schjørring, Olav

AU - Steen Rasmussen, Bodil

N1 - Publisher Copyright: © 2021 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

PY - 2021

Y1 - 2021

N2 - Background: Coronavirus disease (COVID-19) primarily affects the lungs and lower airways and may present as hypoxaemic respiratory failure requiring admission to an intensive care unit (ICU) for supportive treatment. Here, supplemental oxygen remains essential for COVID-19 patient management, but the optimal dosage is not defined. We hypothesize that targeting an arterial partial pressure of oxygen of 8 kPa throughout ICU admission is superior to targeting 12 kPa. Methods: The Handling Oxygenation Targets in ICU patients with COVID-19 (HOT-COVID) trial, is an investigator-initiated, pragmatic, multicentre, randomized, parallel-group trial comparing a lower oxygenation target versus a higher oxygenation target in adult ICU patients with COVID-19. The primary outcome is days alive without life-support (use of mechanical ventilation, renal replacement therapy or vasoactive therapy) at day 90. Secondary outcomes are 90-day and 1-year mortality, serious adverse events in the ICU and days alive and out of hospital in the 90-day period, health-related quality-of-life at 1 year, and health economic analyses. One-year follow-up of cognitive and pulmonary function is planned in a subgroup of Danish patients. We will include 780 patients to detect or reject an absolute increase in days alive without life-support of 7 days with an α of 5% and a β of 20%. An interim analysis is planned after 90-day follow-up of 390 patients. Conclusions: The HOT-COVID trial will provide patient-important data on the effect of two oxygenation targets in ICU patients with COVID-19 and hypoxia. This protocol paper describes the background, design and statistical analysis plan for the trial.

AB - Background: Coronavirus disease (COVID-19) primarily affects the lungs and lower airways and may present as hypoxaemic respiratory failure requiring admission to an intensive care unit (ICU) for supportive treatment. Here, supplemental oxygen remains essential for COVID-19 patient management, but the optimal dosage is not defined. We hypothesize that targeting an arterial partial pressure of oxygen of 8 kPa throughout ICU admission is superior to targeting 12 kPa. Methods: The Handling Oxygenation Targets in ICU patients with COVID-19 (HOT-COVID) trial, is an investigator-initiated, pragmatic, multicentre, randomized, parallel-group trial comparing a lower oxygenation target versus a higher oxygenation target in adult ICU patients with COVID-19. The primary outcome is days alive without life-support (use of mechanical ventilation, renal replacement therapy or vasoactive therapy) at day 90. Secondary outcomes are 90-day and 1-year mortality, serious adverse events in the ICU and days alive and out of hospital in the 90-day period, health-related quality-of-life at 1 year, and health economic analyses. One-year follow-up of cognitive and pulmonary function is planned in a subgroup of Danish patients. We will include 780 patients to detect or reject an absolute increase in days alive without life-support of 7 days with an α of 5% and a β of 20%. An interim analysis is planned after 90-day follow-up of 390 patients. Conclusions: The HOT-COVID trial will provide patient-important data on the effect of two oxygenation targets in ICU patients with COVID-19 and hypoxia. This protocol paper describes the background, design and statistical analysis plan for the trial.

KW - COVID-19

KW - hypoxia

KW - intensive care units

KW - oxygen

U2 - 10.1111/aas.13956

DO - 10.1111/aas.13956

M3 - Journal article

C2 - 34310694

AN - SCOPUS:85112238395

VL - 65

SP - 1497

EP - 1504

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 10

ER -