HOT-COVID: Handling Oxygenation Targets in COVID-19
Study Details
Study Description
Brief 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. 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 4 |
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
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Low oxygenation target Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg) |
Drug: Oxygen
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
Other Names:
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Active Comparator: High oxygenation target Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg) |
Drug: Oxygen
Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge
Other Names:
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Outcome Measures
Primary Outcome Measures
- Days alive without organ support [Within 90 days]
Days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Secondary Outcome Measures
- 90-days mortality [90 days]
All-cause mortality 90 days after randomisation
- Days alive out of the hospital [Within 90 days]
Days alive out of the hospital
- Number of patients with one or more serious adverse events [Until ICU discharge, maximum 90 days]
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 [1 year]
All-cause mortality 1 year after randomisation
- Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview [1 year]
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 [1 year]
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.
- Carbon monoxide diffusion capacity [1 year]
Carbon monoxide diffusion capacity (DLCO) 1 year after randomisation at selected sites.
- A health economic analysis [90 days]
Cost-effectiveness versus cost-minimisation analyses after completion of the trial, based on the primary outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Acutely admitted to the ICU AND
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Aged ≥ 18 years AND
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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
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Expected to receive supplemental oxygen for at least 24 hours in the ICU AND
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Having an arterial line for PaO2 monitoring AND
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Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) in the time leading to or during current hospital admission
Exclusion Criteria:
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Cannot be randomised within twelve hours after present ICU admission
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Chronic mechanical ventilation for any reason
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Use of home oxygen
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Previous treatment with bleomycin
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Organ transplant during current hospital admission
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Withdrawal from active therapy or brain death deemed imminent
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Fertile woman (< 50 years of age) with positive urine human gonadotropin (hCG) or plasma-hCG
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Carbon monoxide poisoning
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Cyanide poisoning
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Methaemoglobinaemia
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Paraquat poisoning
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Any condition expected to involve the use of hyperbaric oxygen (HBO)
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Sickle cell disease
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Consent not obtainable according to national regulations
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Previously randomised into the HOT-COVID trial
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Dept. of Intensive Care, Aalborg University Hospital | Aalborg | Denmark | 9000 | |
2 | Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet | Copenhagen | Denmark | 2100 | |
3 | Dept. of Intensive Care, Herlev Hospital | Herlev | Denmark | 2730 | |
4 | Dept. of Intensive Care, Hillerød Hospital | Hillerød | Denmark | 3400 | |
5 | Dept. of Intensive Care, Kolding Hospital | Kolding | Denmark | 6000 | |
6 | Dept. of Intensive Care, Køge Hospital | Køge | Denmark | 4600 | |
7 | Randers Hospital | Randers | Denmark | 8930 | |
8 | Dept. of Intensive Care, Slagelse Hospital | Slagelse | Denmark | 4200 | |
9 | Oslo University Hospital | Oslo | Norway | ||
10 | Universitätsspital Basel | Basel | Switzerland | 4031 |
Sponsors and Collaborators
- Aalborg University Hospital
- Rigshospitalet, Denmark
- Copenhagen Trial Unit, Center for Clinical Intervention Research
Investigators
- Principal Investigator: Bodil Steen Rasmussen, MD, PhD, Aalborg University Hospital, Denmark
- Study Chair: Bodil Steen Rasmussen, MD, PhD, Aalborg University Hospital, Denmark
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Barbateskovic M, Schjørring 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.
- Barbateskovic M, Schjørring 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). doi: 10.1002/14651858.CD012631.pub2.
- Rasmussen BS, Perner A, Wetterslev J, Meyhoff CS, Schjørring 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.
- Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Keus F, Laake JH, Morgan M, Bäcklund 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.
- Schjørring 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.
- AAUH-ICU-03
- 2017-000632-34