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)
Drug: Oxygen
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
Other Name: Inspired oxygen
Drug: Oxygen
Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge
Other Name: Inspired oxygen
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
Dept. of Intensive Care, Aalborg University Hospital
Aalborg, Denmark
Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
Copenhagen, Denmark
Dept. of Intensive Care, Herlev Hospital
Herlev, Denmark
Dept. of Intensive Care, Hillerød Hospital
Hillerød, Denmark
Dept. of Intensive Care, Kolding Hospital
Kolding, Denmark
Dept. of Intensive Care, Køge Hospital
Køge, Denmark
Randers Hospital
Randers, Denmark
Dept. of Intensive Care, Slagelse Hospital
Slagelse, Denmark
Oslo University Hospital
Oslo, Norway
Universitätsspital Basel
Basel, Switzerland