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Hypoxemic Respiratory FailurePhase 4HOT-ICUNCT03174002

Handling Oxygenation Targets in the Intensive Care Unit

A Phase 4 study testing Oxygen in people with Hypoxemic Respiratory Failure and Oxygen Toxicity, run by Aalborg University Hospital at 37 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Oxygen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,928 participants
Where
37 sitesin 7 countries
Study dates
19 Jun 2017to 3 Aug 2021
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

37 sites in 7 countries.

37 sites in 7 countries

Denmark21 sites

  • Dept. of Intensive Care, Aalborg University Hospital

    Aalborg, 9000

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

    Aarhus, 8000

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

    Aarhus, 8000

  • Dept. of Intensive Care, University Hospital Skejby

    Aarhus, 8200

  • Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet

    Copenhagen, 2100

  • Dept. of Intensive Care, Bispebjerg Hospital

    Copenhagen, 2400

  • Dept. of Intensive Care, Herlev Hospital

    Herlev, 2730

  • Dept. of Intensive Care, Herning Hospital

    Herning, 7400

  • Dept. of Intensive Care, Hillerød Hospital

    Hillerød, 3400

  • Dept. of Intensive Care, Hjørring Hospital

    Hjørring, 9800

  • Dept. of Intensive Care, Holbæk Hospital

    Holbæk, 4300

  • Department of Intensive Care, Holstebro

    Holstebro, 7500

  • Dept. of Intensive Care, Holstebro Hospital

    Holstebro, 7500

  • Dept. of Intensive Care, Horsens Hospital

    Horsens, 8700

  • Dept. of Intensive Care, Hvidovre Hospital

    Hvidovre, 2650

  • Dept. of Intensive Care, Køge Hospital

    Køge, 4600

  • Dept. of Intensive Care, Kolding Hospital

    Kolding, 6000

  • Dept. of Intensive Care, Randers Hospital

    Randers, 8930

  • Dept. of Intensive Care, Roskilde Hospital

    Roskilde, 4000

  • Dept. of Intensive Care, Slagelse Hospital

    Slagelse, 4200

  • Department of Intensive Care, Viborg Hospital

    Viborg, 8800

Other trials in Denmark

United Kingdom6 sites

  • Department of Intensive Care, University Hospital of Wales

    Cardiff, Wales

  • Kingston Hospital NHS Foundation Trust

    Kingston upon Thames, KT2 7QB

  • Royal Glamorgan Hospital

    Llantrisant, CF72 8XR

  • Manchester University NHS Foundation Trust

    Manchester, M13 9WL

  • Wythenshawe Hospital

    Manchester, M23 9LT

  • Royal Berkshire NHS Foundation Trust

    Reading, Berkshire, RG1 5AN

Other trials in United Kingdom

Finland4 sites

  • Dept. of Intensive Care, Helsinki University Hospital

    Helsinki

  • Dept. of Intensive Care, Central Finland Central Hospital

    Jyväskylä, 40620

  • Dept. of Intensive Care, Kuopio University Hospital, Kuopio

    Kuopio, 70210

  • Dept. of Intensive Care, Turku University Hospital, Turku

    Turku, 20520

Other trials in Finland

Netherlands2 sites

  • Dept. of Intensive Care, University Medical Center Groningen

    Groningen, 9713

  • Dept. of Intensive Care, Canisius Wilhelmina Hospital

    Nijmegen, 6532 SZ

Other trials in Netherlands

Switzerland2 sites

  • Dept. of Intensive Care, Basel University Hospital

    Basel, 4056

  • Dept. of Intensive Care, Bern University Hospital

    Bern, 3010

Other trials in Switzerland

Iceland1 site

  • Dept. of Intensive Care, Landspitali University Hospital Reykjavik

    Reykjavik

Other trials in Iceland

Norway1 site

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

    Oslo

Other trials in Norway

About this study

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

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.

Read the 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.

Being tested
Oxygen
Keywords
Oxygenation, Acute Respiratory Distress Syndrome, Mechanical ventilation, Critical illness, Critical care
Medical subject headings
Respiratory Insufficiency, Respiratory Distress Syndrome, Critical Illness

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OxygenDrug

    Also called Inspired oxygen

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

  • OxygenDrug

    Also called Inspired oxygen

    Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge

Study groups in NCT03174002
Study groupRoleWhat they receive
Low oxygenation targetExperimentalPartial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg)
Receives: Drug: Oxygen
High oxygenation targetActive comparatorPartial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg)
Receives: Drug: Oxygen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 90-days mortality

    Landmark mortality 90-days after randomisation

    Measured: 90 days

Secondary outcomes (8)

  1. Days alive without organ support

    Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy

    Measured: Within 90 days

  2. Days alive out of the hospital

    Percentage of days alive out of the hospital

    Measured: Within 90 days

  3. Number of patients with one or more serious adverse events

    Serious adverse events are defined as new episode of shock and new episodes of ischaemic events including myocardial or intestinal ischaemia or ischaemic stroke

    Measured: Until ICU discharge, maximum 90 days

  4. 1-year mortality

    Landmark mortality 1 year after randomisation

    Measured: 1 year

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

    EQ-5D-5L 1-year after randomisation

    Measured: 1 year

  6. Cognitive function 1-year after randomisation as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score in selected sites

    RBANS score 1 year after randomisation at selected sites

    Measured: 1 year

  7. Pulmonary function

    Bodyplethysmography and carbon monooxide diffusion capacity 1 year after randomisation at sellected sites

    Measured: 1 year

  8. A health economic analysis

    The analytic details will be based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses)

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2017
  2. Study start19 Jun 2017
  3. Primary completion3 Nov 2020
  4. Study completion3 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
2,928 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03174002
Sponsor's protocol ID
AAUH-ICU-01
Other IDs
2017-000632-34, 2017
Acronym
HOT-ICU
Status last verified
Oct 2021
First submitted
30 May 2017
Last updated
26 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All original records (incl. consent forms, eCRFs, and relevant correspondences) will be archived at trial sites for 15 years. The clean electronic trial database file will be delivered to the EudraCT Database and Zenodo (https://zenodo.org/about) and maintained for 15 years and anonymised if requested by the authorities.

Publications

  • 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.

    PubMed 30883686

  • 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.

    PubMed 29708586

  • 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.

    PubMed 31773728

  • 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.

    PubMed 30527413

  • 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.

    PubMed 32068884

  • Crescioli E, Klitgaard TL, Riis JO, Weinreich UM, Jensen JS, Vestergaard SR, Bunzel AG, Eriksen ASB, Gudbjerg SH, Poulsen LM, Brochner AC, Mortensen CB, Haberlandt T, Meyer CN, Braagaard L, Mortensen J, Lange T, Perner A, Schjorring OL, Rasmussen BS. Oxygenation Targets and Long-Term Cognitive and Pulmonary Functions in Hypoxemic Respiratory Failure: A Clinical Trial. Am J Respir Crit Care Med. 2026 Mar 1;212(3):464-473. doi: 10.1164/rccm.202412-2499OC.

    PubMed 40920961

  • Nielsen FM, Klitgaard TL, Bruun NH, Moller MH, Schjorring OL, Rasmussen BS. Lower or higher oxygenation targets in the intensive care unit: an individual patient data meta-analysis. Intensive Care Med. 2024 Aug;50(8):1275-1286. doi: 10.1007/s00134-024-07523-3. Epub 2024 Jul 11.

    PubMed 38990335

  • 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.

    PubMed 38711834

  • 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.

    PubMed 37588787

  • 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.

    PubMed 37196799

  • 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.

    PubMed 35441849

  • 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.

    PubMed 34674834

  • 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.

    PubMed 34425016

  • 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.

    PubMed 33471452

  • 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.

    PubMed 32659856

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Oxygen in people with Hypoxemic Respiratory Failure and Oxygen Toxicity, run by Aalborg University Hospital at 37 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Denmark, United Kingdom, Finland, Netherlands, Switzerland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

90-days mortality (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03174002, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2021; AzTrials last refreshed its copy on 30 Oct 2026.

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