Handling Oxygenation Targets in the Intensive Care Unit

NCT03174002 | Completed Phase 4 DMC

• 2 other identifiers: AAUH-ICU-012017-000632-34
• Study Type: interventional
• Target: 2,928
• Locations: 7 countries
• Sites: 37

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.

Conditions

Hypoxemic Respiratory Failure; Oxygen Toxicity

Keywords

Oxygenation; Acute Respiratory Distress Syndrome; Mechanical ventilation; Critical illness; Critical care

Outcome Measures

Primary Outcomes (1)

• 90-days mortality

  Landmark mortality 90-days after randomisation

  90 days

Secondary Outcomes (8)

• Days alive without organ support

  Within 90 days

• Days alive out of the hospital

  Within 90 days

• Number of patients with one or more serious adverse events

  Until ICU discharge, maximum 90 days

• 1-year mortality

  1 year

• Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites

  1 year

Study Arms (2)

Low oxygenation target

EXPERIMENTAL

Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg)

Drug: Oxygen

High oxygenation target

ACTIVE COMPARATOR

Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg)

Drug: Oxygen

Interventions

Oxygen DRUG

Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge

Also known as: Inspired oxygen

Low oxygenation target

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aalborg University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator

Study Sites (37)

Dept. of Intensive Care, Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Dept. of Intensive Care East Section, Øst, Skejby, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Dept. of Intensive Care Section Nord, Skejby, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Dept. of Intensive Care, University Hospital Skejby

Aarhus, 8200, Denmark

Location

Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Intensive Care, Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Dept. of Intensive Care, Herlev Hospital

Herlev, 2730, Denmark

Location

Dept. of Intensive Care, Herning Hospital

Herning, 7400, Denmark

Location

Dept. of Intensive Care, Hillerød Hospital

Hillerød, 3400, Denmark

Location

Dept. of Intensive Care, Hjørring Hospital

Hjørring, 9800, Denmark

Location

Dept. of Intensive Care, Holbæk Hospital

Holbæk, 4300, Denmark

Location

Department of Intensive Care, Holstebro

Holstebro, 7500, Denmark

Location

Dept. of Intensive Care, Holstebro Hospital

Holstebro, 7500, Denmark

Location

Dept. of Intensive Care, Horsens Hospital

Horsens, 8700, Denmark

Location

Dept. of Intensive Care, Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

Dept. of Intensive Care, Kolding Hospital

Kolding, 6000, Denmark

Location

Dept. of Intensive Care, Køge Hospital

Køge, 4600, Denmark

Location

Dept. of Intensive Care, Randers Hospital

Randers, 8930, Denmark

Location

Dept. of Intensive Care, Roskilde Hospital

Roskilde, 4000, Denmark

Location

Dept. of Intensive Care, Slagelse Hospital

Slagelse, 4200, Denmark

Location

Department of Intensive Care, Viborg Hospital

Viborg, 8800, Denmark

Location

Dept. of Intensive Care, Helsinki University Hospital

Helsinki, Finland

Location

Dept. of Intensive Care, Central Finland Central Hospital

Jyväskylä, 40620, Finland

Location

Dept. of Intensive Care, Kuopio University Hospital, Kuopio

Kuopio, 70210, Finland

Location

Dept. of Intensive Care, Turku University Hospital, Turku

Turku, 20520, Finland

Location

Dept. of Intensive Care, Landspitali University Hospital Reykjavik

Reykjavik, Iceland

Location

Dept. of Intensive Care, University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Dept. of Intensive Care, Canisius Wilhelmina Hospital

Nijmegen, 6532 SZ, Netherlands

Location

Dept. of Intensive Care, National Hospital, University of Oslo

Oslo, Norway

Location

Dept. of Intensive Care, Basel University Hospital

Basel, 4056, Switzerland

Location

Dept. of Intensive Care, Bern University Hospital

Bern, 3010, Switzerland

Location

Royal Berkshire NHS Foundation Trust

Reading, Berkshire, RG1 5AN, United Kingdom

Location

Department of Intensive Care, University Hospital of Wales

Cardiff, Wales, United Kingdom

Location

Kingston Hospital NHS Foundation Trust

Kingston upon Thames, KT2 7QB, United Kingdom

Location

Royal Glamorgan Hospital

Llantrisant, CF72 8XR, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Related Publications (13)

• 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.

  PMID: 30883686 BACKGROUND

• 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.

  PMID: 29708586 BACKGROUND

• 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.

  PMID: 31773728 BACKGROUND

• 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.

  PMID: 30527413 BACKGROUND

• 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.

  PMID: 32068884 BACKGROUND

• Nielsen MB, Klitgaard TL, Weinreich UM, Nielsen FM, Perner A, Schjorring OL, Rasmussen BS. Effects of a lower versus a higher oxygenation target in intensive care unit patients with chronic obstructive pulmonary disease and acute hypoxaemic respiratory failure: a subgroup analysis of a randomised clinical trial. BJA Open. 2024 Apr 29;10:100281. doi: 10.1016/j.bjao.2024.100281. eCollection 2024 Jun.

  PMID: 38711834 DERIVED

• Klitgaard TL, Schjorring OL, Severinsen MT, Perner A, Rasmussen BS. Lower versus higher oxygenation targets in ICU patients with haematological malignancy - insights from the HOT-ICU trial. BJA Open. 2022 Sep 23;4:100090. doi: 10.1016/j.bjao.2022.100090. eCollection 2022 Dec.

  PMID: 37588787 DERIVED

• Crescioli E, Lass Klitgaard T, Perner A, Lilleholt Schjorring O, Steen Rasmussen B. Lower versus higher oxygenation targets in hypoxaemic ICU patients after cardiac arrest. Resuscitation. 2023 Jul;188:109838. doi: 10.1016/j.resuscitation.2023.109838. Epub 2023 May 16.

  PMID: 37196799 DERIVED

• 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.

  PMID: 35441849 DERIVED

• 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.

  PMID: 34674834 DERIVED

• 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.

  PMID: 34425016 DERIVED

• 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.

  PMID: 33471452 DERIVED

• 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.

  PMID: 32659856 DERIVED

Related Links

• Link to the HOT-ICU website

MeSH Terms

Conditions

Respiratory Insufficiency; Respiratory Distress Syndrome; Critical Illness

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Study Officials

• Bodil Steen Rasmussen, MD, PhD

  Aalborg University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

• Anders Perner, MD, PhD

  Rigshospitalet, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor, MD, PhD

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 2, 2017
• Study Start: June 19, 2017
• Primary Completion: November 3, 2020
• Study Completion: August 3, 2021
• Last Updated: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Study Protocol and Statistical Analysis Plan has been published. Informed Consent Form are available on the webpage (www.cric.nu/hot-icu)
• Access Criteria: Managed by the Steering Committee of the HOT-ICUT trial.

Locations

GB (6); FI (4); DK (21); IC (1); CH (2); NO (1); NL (2)