Hypoxemic Respiratory FailurePhase 4HOT-COVIDNCT04425031
Handling Oxygenation Targets in COVID-19
A Phase 4 study testing Low oxygenation target and High oxygenation target in people with Hypoxemic Respiratory Failure and Oxygen Toxicity, run by Aalborg University Hospital at 10 sites in 3 countries.
Trial summary
Patients with COVID-19 and hypoxaemic respiratory failure and admitted to the intensive care unit (ICU) are treated with supplementary oxygen as a standard. However, quality of quantity evidence regarding this practise is low. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypoxemic Respiratory Failure, Oxygen Toxicity
- What is being tested?
- Low oxygenation target and High oxygenation target
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 726 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 25 Aug 2020to 8 Mar 2024
- 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 recieves supplemental oxygen in a closed system including invasive or non-invasive ventilation or continuous positive airway pressure (CPAP)-systems AND
- Expected to receive supplemental oxygen for at least 24 hours in the ICU AND
- Having an arterial line for PaO2 monitoring AND
- Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in the time leading to or during current hospital admission
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-COVID trial
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Denmark8 sites
Dept. of Intensive Care, Aalborg University Hospital
Aalborg, 9000
Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
Copenhagen, 2100
Dept. of Intensive Care, Herlev Hospital
Herlev, 2730
Dept. of Intensive Care, Hillerød Hospital
Hillerød, 3400
Dept. of Intensive Care, Køge Hospital
Køge, 4600
Dept. of Intensive Care, Kolding Hospital
Kolding, 6000
Randers Hospital
Randers, 8930
Dept. of Intensive Care, Slagelse Hospital
Slagelse, 4200
About this study
Official title: Handling Oxygenation Targets in COVID-19 Patients With Acute Hypoxaemic Respiratory Failure in the Intensive Care Unit: A Randomised Clinical Trial of a Lower Versus a Higher Oxygenation Target
Patients with COVID-19 and hypoxaemic respiratory failure and admitted to the intensive care unit (ICU) are treated with supplementary oxygen as a standard. However, quality of quantity evidence regarding this practise is low. The aim of the HOT-COVID trial is to evaluate the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen therapy in acutely ill adult COVID-19 patients with hypoxaemic respiratory failure at ICU admission.
Read the detailed description
Acutely ill adult COVID-19 patients with hypoxaemic respiratory failure admitted to the intensive care unit (ICU) are at risk of life-threatening hypoxia, and are provided supplementary oxygen. Liberal use of supplementary oxygen may increase the number of serious adverse events including death. However, the use of supplementary oxygen therapy, and the optimal oxygenation target in COVID-19 patients have not yet been studied.
The World Health Organisation (WHO) recommends an oxygen therapy during resuscitation of COVID-19 patients to achieve an SpO2 of 94% or more, and 90% or more when stable (non-pregnant patients). The Surviving Sepsis Campaing (SSC) recommends a conservative oxygenation strategy for COVID-19 patients targeting an SpO2 no higher than 96%. Both are based on a systematic review and metanalysis from 2018, investigating the association with mortality and higher versus lower oxygenation strategies in critically ill patients in general.
COVID-19 patients admitted to the ICU and treated with positive pressure ventilation fulfil the 2012 Berlin criteria for acute respiratory distress syndrome (ARDS). Current practice regarding supplementary oxygen therapy in patients with ARDS follows the regimen used in an randomised clinical trial (RCT) from 2000 comparing lower versus higher tidal volumes; i.e. a partial pressure of arterial oxygen (PaO2) of 55-80 mmHg (7.3-10.7 kPa) or a peripheral oxygen saturation (SpO2) of 88-95%.
Of note, a recent published RCT demonstrated a lowered all-cause mortality when targeting a higher oxygenation target (PaO2: 12-14 kPa [90-105 mmHg]) compared to a lower oxygenation target (PaO2: 7.3-9.3 [55-70 mmHg]) in ARDS patients.
The quality and quantity of the current body of evidence regarding oxygenation targets in ARDS is still low.
The aim of the HOT-COVID trial is to evaluate the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen therapy in acutely ill adults COVID-19 patients with hypoxaemic respiratory failure at ICU admission.
The HOT-COVID trial is an amendment to the HOT-ICU trial (NCT03174002)
- Conditions
- Hypoxemic Respiratory Failure, Oxygen Toxicity
- Being tested
- Low oxygenation target, High oxygenation target
- 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.
Low oxygenation targetDrug
Also called Inspired oxygen
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
High oxygenation targetDrug
Also called Inspired oxygen
Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge
| Study group | Role | What they receive |
|---|---|---|
| Low oxygenation target | Experimental | Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg) Receives: Drug: Low oxygenation target |
| High oxygenation target | Active comparator | Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg) Receives: Drug: High oxygenation target |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive without organ support
Days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Measured: Within 90 days
Secondary outcomes (8)
90-days mortality
All-cause mortality 90 days after randomisation
Measured: 90 days
Days alive out of the hospital
Days alive out of the hospital
Measured: Within 90 days
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
1-year mortality
All-cause mortality 1 year after randomisation
Measured: 1 year
Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview
EQ-5D-5L 1-year after randomisation
Measured: 1 year
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. The overall RBANS global cognition score, as well as each cognitive domain score, range from 40 to 160 with 100 ± 15 being the age-adjusted mean ± standard deviation. Higher scores indicate better performance.
Measured: 1 year
Carbon monoxide diffusion capacity
Carbon monoxide diffusion capacity (DLCO) 1 year after randomisation at selected sites.
Measured: 1 year
A health economic analysis
Cost-effectiveness versus cost-minimisation analyses after completion of the trial, based on the primary outcome.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start25 Aug 2020
- Primary completion8 Mar 2023
- Study completion8 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Hypoxemic Respiratory FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 726 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Copenhagen Trial Unit, Center for Clinical Intervention Research
- Responsible party
- Principal investigator, Bodil Steen Rasmussen, Aalborg University Hospital
- Investigators
- Bodil Steen Rasmussen, MD, PhD, Principal investigator, Aalborg University HospitalBodil Steen Rasmussen, MD, PhD, Study chair, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425031
- Sponsor's protocol ID
- AAUH-ICU-03
- Other IDs
- 2017-000632-34, 2017
- Acronym
- HOT-COVID
- Status last verified
- Jul 2024
- First submitted
- 5 Jun 2020
- Last updated
- 15 Jul 2024
- 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, electronic clinical report 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 data repository (https://zenodo.org/) 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 30883686Barbateskovic 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 29708586Barbateskovic 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 31773728Rasmussen 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 30527413Schjorring 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 32068884Nielsen 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 38990335Nielsen FM, Klitgaard TL, Siegemund M, Laake JH, Thormar KM, Cole JM, Aagaard SR, Bunzel AG, Vestergaard SR, Langhoff PK, Pedersen CH, Hejlesen JO, Abdelhamid S, Dietz A, Gebhard CE, Zellweger N, Hollinger A, Poulsen LM, Weihe S, Andersen-Ranberg NC, Pedersen UG, Mathiesen O, Andreasen AS, Brix H, Thomsen JJ, Petersen CH, Bestle MH, Wichmann S, Lund MS, Mortensen KM, Brand BA, Haase N, Iversen SA, Marcussen KV, Brochner AC, Borup M, Grofte T, Hildebrandt T, Kjaer MN, Engstrom J, Lange T, Perner A, Schjorring OL, Rasmussen BS; HOT-COVID Trial Group. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA. 2024 Apr 9;331(14):1185-1194. doi: 10.1001/jama.2024.2934.
PubMed 38501214Crescioli 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 40920961Nielsen FM, Klitgaard TL, Granholm A, Lange T, Perner A, Schjorring OL, Rasmussen BS. Lower or Higher Oxygenation Targets in Patients With COVID-19 in the ICU: A Secondary Bayesian Analysis of the Handling Oxygenation Targets in COVID-19 Trial. Chest. 2025 Mar;167(3):757-767. doi: 10.1016/j.chest.2024.08.055. Epub 2024 Sep 18.
PubMed 39303806
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Handling Oxygenation Targets in COVID-19 Patients With Acute Hypoxaemic Respiratory Failure in the Intensive Care Unit: A Randomised Clinical Trial of a Lower Versus a Higher Oxygenation Target
- ClinicalTrials.gov ID
- NCT04425031
- Acronym / sponsor ID
- HOT-COVID / AAUH-ICU-03
- Conditions
- Hypoxemic Respiratory Failure, Oxygen Toxicity
- Keywords
- Oxygenation, Acute Respiratory Distress Syndrome, Mechanical ventilation, Critical illness, Critical care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 726 participants (actual)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Copenhagen Trial Unit, Center for Clinical Intervention Research
- Study start
- 25 Aug 2020 (actual)
- Primary completion
- 8 Mar 2023 (actual)
- Study completion
- 8 Mar 2024 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with COVID-19 and hypoxaemic respiratory failure and admitted to the intensive care unit (ICU) are treated with supplementary oxygen as a standard. However, quality of quantity evidence regarding this practise is low. The aim of the HOT-COVID trial is to evaluate the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen therapy in acutely ill adult COVID-19 patients with hypoxaemic respiratory failure at ICU admission.
Detailed description
Acutely ill adult COVID-19 patients with hypoxaemic respiratory failure admitted to the intensive care unit (ICU) are at risk of life-threatening hypoxia, and are provided supplementary oxygen. Liberal use of supplementary oxygen may increase the number of serious adverse events including death. However, the use of supplementary oxygen therapy, and the optimal oxygenation target in COVID-19 patients have not yet been studied.
The World Health Organisation (WHO) recommends an oxygen therapy during resuscitation of COVID-19 patients to achieve an SpO2 of 94% or more, and 90% or more when stable (non-pregnant patients). The Surviving Sepsis Campaing (SSC) recommends a conservative oxygenation strategy for COVID-19 patients targeting an SpO2 no higher than 96%. Both are based on a systematic review and metanalysis from 2018, investigating the association with mortality and higher versus lower oxygenation strategies in critically ill patients in general.
COVID-19 patients admitted to the ICU and treated with positive pressure ventilation fulfil the 2012 Berlin criteria for acute respiratory distress syndrome (ARDS). Current practice regarding supplementary oxygen therapy in patients with ARDS follows the regimen used in an randomised clinical trial (RCT) from 2000 comparing lower versus higher tidal volumes; i.e. a partial pressure of arterial oxygen (PaO2) of 55-80 mmHg (7.3-10.7 kPa) or a peripheral oxygen saturation (SpO2) of 88-95%.
Of note, a recent published RCT demonstrated a lowered all-cause mortality when targeting a higher oxygenation target (PaO2: 12-14 kPa [90-105 mmHg]) compared to a lower oxygenation target (PaO2: 7.3-9.3 [55-70 mmHg]) in ARDS patients.
The quality and quantity of the current body of evidence regarding oxygenation targets in ARDS is still low.
The aim of the HOT-COVID trial is to evaluate the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen therapy in acutely ill adults COVID-19 patients with hypoxaemic respiratory failure at ICU admission.
The HOT-COVID trial is an amendment to the HOT-ICU trial (NCT03174002)
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low oxygenation target | Experimental | Drug: Low oxygenation targetPartial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg) |
| High oxygenation target | Active comparator | Drug: High oxygenation targetPartial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 recieves supplemental oxygen in a closed system including invasive or non-invasive ventilation or continuous positive airway pressure (CPAP)-systems AND
- Expected to receive supplemental oxygen for at least 24 hours in the ICU AND
- Having an arterial line for PaO2 monitoring AND
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low oxygenation targetAlso: Inspired oxygenOxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge | Drug | Low oxygenation target |
| High oxygenation targetAlso: Inspired oxygenOxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge | Drug | High oxygenation target |
Primary outcome
Days alive without organ support
Time frame: Within 90 days
Days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
8 secondary outcomes
90-days mortality
Time frame: 90 days
Days alive out of the hospital
Time frame: Within 90 days
Number of patients with one or more serious adverse events
Time frame: Until ICU discharge, maximum 90 days
1-year mortality
Time frame: 1 year
Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview
Time frame: 1 year
Cognitive function 1-year after randomisation as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score in selected sites
Time frame: 1 year
Carbon monoxide diffusion capacity
Time frame: 1 year
A health economic analysis
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2024.
- Background: PubMed 30883686Schjorring 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.
- Background: PubMed 29708586Barbateskovic 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.
- Background: PubMed 31773728Barbateskovic 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.
- Background: PubMed 30527413Rasmussen 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.
- Background: PubMed 32068884Schjorring 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 publication: PubMed 38990335Nielsen 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.
- Results publication: PubMed 38501214Nielsen FM, Klitgaard TL, Siegemund M, Laake JH, Thormar KM, Cole JM, Aagaard SR, Bunzel AG, Vestergaard SR, Langhoff PK, Pedersen CH, Hejlesen JO, Abdelhamid S, Dietz A, Gebhard CE, Zellweger N, Hollinger A, Poulsen LM, Weihe S, Andersen-Ranberg NC, Pedersen UG, Mathiesen O, Andreasen AS, Brix H, Thomsen JJ, Petersen CH, Bestle MH, Wichmann S, Lund MS, Mortensen KM, Brand BA, Haase N, Iversen SA, Marcussen KV, Brochner AC, Borup M, Grofte T, Hildebrandt T, Kjaer MN, Engstrom J, Lange T, Perner A, Schjorring OL, Rasmussen BS; HOT-COVID Trial Group. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA. 2024 Apr 9;331(14):1185-1194. doi: 10.1001/jama.2024.2934.
- Derived from this study: PubMed 40920961Crescioli 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.
- Derived from this study: PubMed 39303806Nielsen FM, Klitgaard TL, Granholm A, Lange T, Perner A, Schjorring OL, Rasmussen BS. Lower or Higher Oxygenation Targets in Patients With COVID-19 in the ICU: A Secondary Bayesian Analysis of the Handling Oxygenation Targets in COVID-19 Trial. Chest. 2025 Mar;167(3):757-767. doi: 10.1016/j.chest.2024.08.055. Epub 2024 Sep 18.
- Link to the HOT-COVID websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All original records (incl. consent forms, electronic clinical report 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 data repository (https://zenodo.org/) and maintained for 15 years and anonymised if requested by the authorities.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bodil Steen Rasmussen, MD, PhD principal investigator
Aalborg University Hospital
Bodil Steen Rasmussen, MD, PhD study chair
Aalborg University Hospital
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low oxygenation target and High oxygenation target in people with Hypoxemic Respiratory Failure and Oxygen Toxicity, run by Aalborg University Hospital at 10 sites in 3 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 6 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 15 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Denmark, Norway, Switzerland. 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?
Days alive without organ support (time frame: Within 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 NCT04425031, which also lists 9 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 15 Jul 2024.