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Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU)

Primary Purpose

Hypoxemic Respiratory Failure, Oxygen Toxicity

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Oxygen
Oxygen
Sponsored by
Aalborg University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hypoxemic Respiratory Failure focused on measuring Oxygenation, Acute Respiratory Distress Syndrome, Mechanical ventilation, Critical illness, Critical care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dept. of Intensive Care, Aalborg University Hospital
  • Dept. of Intensive Care East Section, Øst, Skejby, Aarhus University Hospital
  • Dept. of Intensive Care Section Nord, Skejby, Aarhus University Hospital
  • Dept. of Intensive Care, University Hospital Skejby
  • Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
  • Dept. of Intensive Care, Bispebjerg Hospital
  • Dept. of Intensive Care, Herlev Hospital
  • Dept. of Intensive Care, Herning Hospital
  • Dept. of Intensive Care, Hillerød Hospital
  • Dept. of Intensive Care, Hjørring Hospital
  • Dept. of Intensive Care, Holbæk Hospital
  • Department of Intensive Care, Holstebro
  • Dept. of Intensive Care, Holstebro Hospital
  • Dept. of Intensive Care, Horsens Hospital
  • Dept. of Intensive Care, Hvidovre Hospital
  • Dept. of Intensive Care, Kolding Hospital
  • Dept. of Intensive Care, Køge Hospital
  • Dept. of Intensive Care, Randers Hospital
  • Dept. of Intensive Care, Roskilde Hospital
  • Dept. of Intensive Care, Slagelse Hospital
  • Department of Intensive Care, Viborg Hospital
  • Dept. of Intensive Care, Helsinki University Hospital
  • Dept. of Intensive Care, Central Finland Central Hospital
  • Dept. of Intensive Care, Kuopio University Hospital, Kuopio
  • Dept. of Intensive Care, Turku University Hospital, Turku
  • Dept. of Intensive Care, Landspitali University Hospital Reykjavik
  • Dept. of Intensive Care, University Medical Center Groningen
  • Dept. of Intensive Care, Canisius Wilhelmina Hospital
  • Dept. of Intensive Care, National Hospital, University of Oslo
  • Dept. of Intensive Care, Basel University Hospital
  • Dept. of Intensive Care, Bern University Hospital
  • Royal Berkshire NHS Foundation Trust
  • Department of Intensive Care, University Hospital of Wales
  • Kingston Hospital NHS Foundation Trust
  • Royal Glamorgan Hospital
  • Manchester University NHS Foundation Trust
  • Wythenshawe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Low oxygenation target

High oxygenation target

Arm Description

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

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

Outcomes

Primary Outcome Measures

90-days mortality
Landmark mortality 90-days after randomisation

Secondary Outcome Measures

Days alive without organ support
Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Days alive out of the hospital
Percentage of days alive out of the hospital
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
1-year mortality
Landmark mortality 1 year after randomisation
Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites
EQ-5D-5L 1-year after randomisation
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
Pulmonary function
Bodyplethysmography and carbon monooxide diffusion capacity 1 year after randomisation at sellected sites
A health economic analysis
The analytic details will be based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses)

Full Information

First Posted
May 30, 2017
Last Updated
October 24, 2021
Sponsor
Aalborg University Hospital
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research
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1. Study Identification

Unique Protocol Identification Number
NCT03174002
Brief Title
Handling Oxygenation Targets in the Intensive Care Unit
Acronym
HOT-ICU
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

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
June 19, 2017 (Actual)
Primary Completion Date
November 3, 2020 (Actual)
Study Completion Date
August 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aalborg University Hospital
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxemic Respiratory Failure, Oxygen Toxicity
Keywords
Oxygenation, Acute Respiratory Distress Syndrome, Mechanical ventilation, Critical illness, Critical care

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
2928 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low oxygenation target
Arm Type
Experimental
Arm Description
Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg)
Arm Title
High oxygenation target
Arm Type
Active Comparator
Arm Description
Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg)
Intervention Type
Drug
Intervention Name(s)
Oxygen
Other Intervention Name(s)
Inspired oxygen
Intervention Description
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
Intervention Type
Drug
Intervention Name(s)
Oxygen
Other Intervention Name(s)
Inspired oxygen
Intervention Description
Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge
Primary Outcome Measure Information:
Title
90-days mortality
Description
Landmark mortality 90-days after randomisation
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Days alive without organ support
Description
Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Time Frame
Within 90 days
Title
Days alive out of the hospital
Description
Percentage of days alive out of the hospital
Time Frame
Within 90 days
Title
Number of patients with one or more serious adverse events
Description
Serious adverse events are defined as new episode of shock and new episodes of ischaemic events including myocardial or intestinal ischaemia or ischaemic stroke
Time Frame
Until ICU discharge, maximum 90 days
Title
1-year mortality
Description
Landmark mortality 1 year after randomisation
Time Frame
1 year
Title
Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites
Description
EQ-5D-5L 1-year after randomisation
Time Frame
1 year
Title
Cognitive function 1-year after randomisation as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score in selected sites
Description
RBANS score 1 year after randomisation at selected sites
Time Frame
1 year
Title
Pulmonary function
Description
Bodyplethysmography and carbon monooxide diffusion capacity 1 year after randomisation at sellected sites
Time Frame
1 year
Title
A health economic analysis
Description
The analytic details will be based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses)
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bodil Steen Rasmussen, MD, PhD
Organizational Affiliation
Aalborg University Hospital, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anders Perner, MD, PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Study Chair
Facility Information:
Facility Name
Dept. of Intensive Care, Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Dept. of Intensive Care East Section, Øst, Skejby, Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Dept. of Intensive Care Section Nord, Skejby, Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Dept. of Intensive Care, University Hospital Skejby
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Dept. of Intensive Care, Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Dept. of Intensive Care, Herlev Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Dept. of Intensive Care, Herning Hospital
City
Herning
ZIP/Postal Code
7400
Country
Denmark
Facility Name
Dept. of Intensive Care, Hillerød Hospital
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Dept. of Intensive Care, Hjørring Hospital
City
Hjørring
ZIP/Postal Code
9800
Country
Denmark
Facility Name
Dept. of Intensive Care, Holbæk Hospital
City
Holbæk
ZIP/Postal Code
4300
Country
Denmark
Facility Name
Department of Intensive Care, Holstebro
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark
Facility Name
Dept. of Intensive Care, Holstebro Hospital
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark
Facility Name
Dept. of Intensive Care, Horsens Hospital
City
Horsens
ZIP/Postal Code
8700
Country
Denmark
Facility Name
Dept. of Intensive Care, Hvidovre Hospital
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Facility Name
Dept. of Intensive Care, Kolding Hospital
City
Kolding
ZIP/Postal Code
6000
Country
Denmark
Facility Name
Dept. of Intensive Care, Køge Hospital
City
Køge
ZIP/Postal Code
4600
Country
Denmark
Facility Name
Dept. of Intensive Care, Randers Hospital
City
Randers
ZIP/Postal Code
8930
Country
Denmark
Facility Name
Dept. of Intensive Care, Roskilde Hospital
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Facility Name
Dept. of Intensive Care, Slagelse Hospital
City
Slagelse
ZIP/Postal Code
4200
Country
Denmark
Facility Name
Department of Intensive Care, Viborg Hospital
City
Viborg
ZIP/Postal Code
8800
Country
Denmark
Facility Name
Dept. of Intensive Care, Helsinki University Hospital
City
Helsinki
Country
Finland
Facility Name
Dept. of Intensive Care, Central Finland Central Hospital
City
Jyväskylä
ZIP/Postal Code
40620
Country
Finland
Facility Name
Dept. of Intensive Care, Kuopio University Hospital, Kuopio
City
Kuopio
ZIP/Postal Code
70210
Country
Finland
Facility Name
Dept. of Intensive Care, Turku University Hospital, Turku
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Dept. of Intensive Care, Landspitali University Hospital Reykjavik
City
Reykjavík
Country
Iceland
Facility Name
Dept. of Intensive Care, University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713
Country
Netherlands
Facility Name
Dept. of Intensive Care, Canisius Wilhelmina Hospital
City
Nijmegen
ZIP/Postal Code
6532 SZ
Country
Netherlands
Facility Name
Dept. of Intensive Care, National Hospital, University of Oslo
City
Oslo
Country
Norway
Facility Name
Dept. of Intensive Care, Basel University Hospital
City
Basel
ZIP/Postal Code
4056
Country
Switzerland
Facility Name
Dept. of Intensive Care, Bern University Hospital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Royal Berkshire NHS Foundation Trust
City
Reading
State/Province
Berkshire
ZIP/Postal Code
RG1 5AN
Country
United Kingdom
Facility Name
Department of Intensive Care, University Hospital of Wales
City
Cardiff
State/Province
Wales
Country
United Kingdom
Facility Name
Kingston Hospital NHS Foundation Trust
City
Kingston Upon Thames
ZIP/Postal Code
KT2 7QB
Country
United Kingdom
Facility Name
Royal Glamorgan Hospital
City
Llantrisant
ZIP/Postal Code
CF72 8XR
Country
United Kingdom
Facility Name
Manchester University NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
Study Protocol and Statistical Analysis Plan has been published. Informed Consent Form are available on the webpage (www.cric.nu/hot-icu)
IPD Sharing Access Criteria
Managed by the Steering Committee of the HOT-ICUT trial.
IPD Sharing URL
https://www.cric.nu/hot-icu/
Citations:
PubMed Identifier
30883686
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.
Results Reference
background
PubMed Identifier
29708586
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.
Results Reference
background
PubMed Identifier
31773728
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.
Results Reference
background
PubMed Identifier
30527413
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.
Results Reference
background
PubMed Identifier
32068884
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.
Results Reference
background
PubMed Identifier
35441849
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.
Results Reference
derived
PubMed Identifier
34674834
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.
Results Reference
derived
PubMed Identifier
34425016
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.
Results Reference
derived
PubMed Identifier
33471452
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.
Results Reference
derived
PubMed Identifier
32659856
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.
Results Reference
derived
Links:
URL
https://www.cric.nu/hot-icu/
Description
Link to the HOT-ICU website

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Handling Oxygenation Targets in the Intensive Care Unit

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