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.

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)

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 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

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-COVID trial

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.

Data will be available from June 2024 and for 10 years ahead.

Access Criteria:

Managed by the Steering Committee of the HOT-COVID trial.