Clinical trial NCT03174002: Handling Oxygenation Targets in the Intensive Care Unit
Official title: Handling Oxygenation Targets in Adults With Acute Hypoxaemic Respiratory Failure in the Intensive Care Unit: A Randomised Clinical Trial of a Lower Versus a Higher Oxygenation Target
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypoxemic Respiratory Failure
Oxygen Toxicity
Keywords: Oxygenation
Acute Respiratory Distress Syndrome
Mechanical ventilation
Critical illness
Critical care
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
First posted: 2017-06-02
Enrollment: 2928
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Handling oxygenation targets (HOT) is standard of care in the intensive care unit (ICU), however the quality and quantity of evidence is low and potential harm has been reported. The aim of the HOT-ICU trial is to assess the overall benefits and harms of two levels of oxygenation targets in adult critically ill patients with acute hypoxaemic respiratory failure in the ICU.

Detailed description: Acutely ill adults with hypoxaemic respiratory failure admitted to the intensive care unit (ICU) are at risk of life-threatening hypoxia, and thus oxygen is administered. However, the evidence on the optimal level of oxygenation is of low quantity and quality with no firm evidence for benefit or harm. Importantly, liberal use of supplementary oxygen may increase the number of serious adverse events including death. The aim of the HOT-ICU trial is to assess the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen administration in acutely ill adults with hypoxaemic respiratory failure at ICU admission.

Eligibility criteria: Inclusion Criteria:

* Acutely admitted to the ICU AND
* Aged ≥ 18 years AND
* Receives supplemental oxygen with a flow of at least 10 L per minutes in an open system including high-flow systems OR at least a FiO2 of 0.50 in a closed system including invasive or non-invasive ventilation or CPAP systems AND
* Expected to receive supplemental oxygen for at least 24 hours in the ICU AND
* Having an arterial line for PaO2 monitoring

Exclusion Criteria:

* Cannot be randomised within twelve hours after present ICU admission
* Chronic mechanical ventilation for any reason
* Use of home oxygen
* Previous treatment with bleomycin
* Organ transplant during current hospital admission
* Withdrawal from active therapy or brain death deemed imminent
* Fertile woman (\< 50 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG
* Carbon monoxide poisoning
* Cyanide poisoning
* Methaemoglobinaemia
* Paraquat poisoning
* Any condition expected to involve the use of hyperbaric oxygen (HBO)
* Sickle cell disease
* Consent not obtainable according to national regulations
* Previously randomised into the HOT-ICU trial

Primary outcomes:
measure: 90-days mortality
timeFrame: 90 days
Secondary outcomes:
measure: Days alive without organ support
timeFrame: Within 90 days
measure: Days alive out of the hospital
timeFrame: Within 90 days
measure: Number of patients with one or more serious adverse events
timeFrame: Until ICU discharge, maximum 90 days
measure: 1-year mortality
timeFrame: 1 year
measure: Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites
timeFrame: 1 year
measure: Cognitive function 1-year after randomisation as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score in selected sites
timeFrame: 1 year
measure: Pulmonary function
timeFrame: 1 year
measure: A health economic analysis
timeFrame: 90 days
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Dept. of Intensive Care, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Dept. of Intensive Care East Section, Øst, Skejby, Aarhus University Hospital
city: Aarhus
country: Denmark
facility: Dept. of Intensive Care Section Nord, Skejby, Aarhus University Hospital
city: Aarhus
country: Denmark
facility: Dept. of Intensive Care, University Hospital Skejby
city: Copenhagen
country: Denmark
facility: Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
city: Copenhagen
country: Denmark
facility: Dept. of Intensive Care, Bispebjerg Hospital
city: Herlev
country: Denmark
facility: Dept. of Intensive Care, Herlev Hospital
city: Herning
country: Denmark
facility: Dept. of Intensive Care, Herning Hospital
city: Hillerød
country: Denmark
facility: Dept. of Intensive Care, Hillerød Hospital
city: Hjørring
country: Denmark
facility: Dept. of Intensive Care, Hjørring Hospital
city: Holbæk
country: Denmark
facility: Dept. of Intensive Care, Holbæk Hospital
city: Holstebro
country: Denmark
facility: Department of Intensive Care, Holstebro
city: Holstebro
country: Denmark
facility: Dept. of Intensive Care, Holstebro Hospital
city: Horsens
country: Denmark
facility: Dept. of Intensive Care, Horsens Hospital
city: Hvidovre
country: Denmark
facility: Dept. of Intensive Care, Hvidovre Hospital
city: Kolding
country: Denmark
facility: Dept. of Intensive Care, Kolding Hospital
city: Køge
country: Denmark
facility: Dept. of Intensive Care, Køge Hospital
city: Randers
country: Denmark
facility: Dept. of Intensive Care, Randers Hospital
city: Roskilde
country: Denmark
facility: Dept. of Intensive Care, Roskilde Hospital
city: Slagelse
country: Denmark
facility: Dept. of Intensive Care, Slagelse Hospital
city: Viborg
country: Denmark
facility: Department of Intensive Care, Viborg Hospital
city: Helsinki
country: Finland
facility: Dept. of Intensive Care, Helsinki University Hospital
city: Jyväskylä
country: Finland
facility: Dept. of Intensive Care, Central Finland Central Hospital
city: Kuopio
country: Finland
facility: Dept. of Intensive Care, Kuopio University Hospital, Kuopio
city: Turku
country: Finland
facility: Dept. of Intensive Care, Turku University Hospital, Turku
city: Reykjavík
country: Iceland
facility: Dept. of Intensive Care, Landspitali University Hospital Reykjavik
city: Groningen
country: Netherlands
facility: Dept. of Intensive Care, University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Dept. of Intensive Care, Canisius Wilhelmina Hospital
city: Oslo
country: Norway
facility: Dept. of Intensive Care, National Hospital, University of Oslo
city: Basel
country: Switzerland
facility: Dept. of Intensive Care, Basel University Hospital
city: Bern
country: Switzerland
facility: Dept. of Intensive Care, Bern University Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
state: Berkshire
city: Cardiff
country: United Kingdom
facility: Department of Intensive Care, University Hospital of Wales
state: Wales
city: Kingston Upon Thames
country: United Kingdom
facility: Kingston Hospital NHS Foundation Trust
city: Llantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
Study officials:
affiliation: Aalborg University Hospital, Denmark
name: Bodil Steen Rasmussen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Anders Perner, MD, PhD
role: STUDY_CHAIR
References:
citation: Schjorring OL, Perner A, Wetterslev J, Lange T, Keus F, Laake JH, Okkonen M, Siegemund M, Morgan M, Thormar KM, Rasmussen BS; HOT-ICU Investigators. Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU)-Protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure. Acta Anaesthesiol Scand. 2019 Aug;63(7):956-965. doi: 10.1111/aas.13356. Epub 2019 Mar 18.
citation: Barbateskovic M, Schjorring OL, Jakobsen JC, Meyhoff CS, Rasmussen BS, Perner A, Wetterslev J. Oxygen supplementation for critically ill patients-A protocol for a systematic review. Acta Anaesthesiol Scand. 2018 Aug;62(7):1020-1030. doi: 10.1111/aas.13127. Epub 2018 Apr 30.
citation: Barbateskovic M, Schjorring OL, Russo Krauss S, Jakobsen JC, Meyhoff CS, Dahl RM, Rasmussen BS, Perner A, Wetterslev J. Higher versus lower fraction of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit. Cochrane Database Syst Rev. 2019 Nov 27;2019(11):CD012631. doi: 10.1002/14651858.CD012631.pub2.
citation: Rasmussen BS, Perner A, Wetterslev J, Meyhoff CS, Schjorring OL. Oxygenation targets in acutely ill patients: still a matter of debate. Lancet. 2018 Dec 8;392(10163):2436-2437. doi: 10.1016/S0140-6736(18)32201-3. No abstract available.
citation: Schjorring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Keus F, Laake JH, Morgan M, Backlund M, Siegemund M, Thormar KM, Rasmussen BS. The handling oxygenation targets in the intensive care unit (HOT-ICU) trial: Detailed statistical analysis plan. Acta Anaesthesiol Scand. 2020 Jul;64(6):847-856. doi: 10.1111/aas.13569. Epub 2020 Mar 4.
citation: Crescioli E, Klitgaard TL, Poulsen LM, Brand BA, Siegemund M, Grofte T, Keus F, Pedersen UG, Backlund M, Karttunen J, Morgan M, Ciubotariu A, Bunzel AG, Vestergaard SR, Jensen NM, Jensen TS, Kjaer MN, Jensen AKG, Lange T, Wetterslev J, Perner A, Schjorring OL, Rasmussen BS. Long-term mortality and health-related quality of life of lower versus higher oxygenation targets in ICU patients with severe hypoxaemia. Intensive Care Med. 2022 Jun;48(6):714-722. doi: 10.1007/s00134-022-06695-0. Epub 2022 Apr 20.
citation: Klitgaard TL, Schjorring OL, Lange T, Moller MH, Perner A, Rasmussen BS, Granholm A. Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia: secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial. Br J Anaesth. 2022 Jan;128(1):55-64. doi: 10.1016/j.bja.2021.09.010. Epub 2021 Oct 19.
citation: Rasmussen BS, Klitgaard TL, Perner A, Brand BA, Hildebrandt T, Siegemund M, Hollinger A, Aagaard SR, Bestle MH, Marcussen KV, Brochner AC, Solling CG, Poulsen LM, Laake JH, Aslam TN, Backlund M, Okkonen M, Morgan M, Sharman M, Lange T, Wetterslev J, Schjorring OL. Oxygenation targets in ICU patients with COVID-19: A post hoc subgroup analysis of the HOT-ICU trial. Acta Anaesthesiol Scand. 2022 Jan;66(1):76-84. doi: 10.1111/aas.13977. Epub 2021 Sep 20.
citation: Schjorring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, Backlund M, Keus F, Laake JH, Morgan M, Thormar KM, Rosborg SA, Bisgaard J, Erntgaard AES, Lynnerup AH, Pedersen RL, Crescioli E, Gielstrup TC, Behzadi MT, Poulsen LM, Estrup S, Laigaard JP, Andersen C, Mortensen CB, Brand BA, White J, Jarnvig IL, Moller MH, Quist L, Bestle MH, Schonemann-Lund M, Kamper MK, Hindborg M, Hollinger A, Gebhard CE, Zellweger N, Meyhoff CS, Hjort M, Bech LK, Grofte T, Bundgaard H, Ostergaard LHM, Thyo MA, Hildebrandt T, Uslu B, Solling CG, Moller-Nielsen N, Brochner AC, Borup M, Okkonen M, Dieperink W, Pedersen UG, Andreasen AS, Buus L, Aslam TN, Winding RR, Schefold JC, Thorup SB, Iversen SA, Engstrom J, Kjaer MN, Rasmussen BS; HOT-ICU Investigators. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med. 2021 Apr 8;384(14):1301-1311. doi: 10.1056/NEJMoa2032510. Epub 2021 Jan 20.
citation: Klitgaard TL, Schjorring OL, Lange T, Moller MH, Perner A, Rasmussen BS, Granholm A. Bayesian and heterogeneity of treatment effect analyses of the HOT-ICU trial-A secondary analysis protocol. Acta Anaesthesiol Scand. 2020 Oct;64(9):1376-1381. doi: 10.1111/aas.13669. Epub 2020 Aug 5.