Handling Oxygenation Targets in COVID-19

Hypoxemic Respiratory Failure Clinical Trial

— HOT-COVID  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04425031
• Other study ID #: AAUH-ICU-03
• Secondary ID: 2017-000632-34
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: August 25, 2020
• Est. completion date: March 8, 2024

Study information

• Verified date: January 2024
• Source: Aalborg University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 726
• Est. completion date: March 8, 2024
• Est. primary completion date: March 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypoxemic Respiratory Failure
• Oxygen Toxicity
• Respiratory Insufficiency

Intervention

Drug:
• Oxygen
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
• Oxygen
Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge

Locations

Country	Name	City	State
Denmark	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, Køge Hospital	Køge
Denmark	Dept. of Intensive Care, Kolding Hospital	Kolding
Denmark	Randers Hospital	Randers
Denmark	Dept. of Intensive Care, Slagelse Hospital	Slagelse
Norway	Oslo University Hospital	Oslo
Switzerland	Universitätsspital Basel	Basel

Sponsors (3)

Lead Sponsor	Collaborator
Aalborg University Hospital	Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Denmark

Countries where clinical trial is conducted

Denmark,  Norway,  Switzerland, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days alive without organ support	Days alive and free from mechanical ventilation, circulatory support and renal replacement therapy	Within 90 days
Secondary	90-days mortality	All-cause mortality 90 days after randomisation	90 days
Secondary	Days alive out of the hospital	Days alive out of the hospital	Within 90 days
Secondary	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	Until ICU discharge, maximum 90 days
Secondary	1-year mortality	All-cause mortality 1 year after randomisation	1 year
Secondary	Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview	EQ-5D-5L 1-year after randomisation	1 year
Secondary	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.	1 year
Secondary	Carbon monoxide diffusion capacity	Carbon monoxide diffusion capacity (DLCO) 1 year after randomisation at selected sites.	1 year
Secondary	A health economic analysis	Cost-effectiveness versus cost-minimisation analyses after completion of the trial, based on the primary outcome.	90 days

External Links

•   Link to the HOT-COVID website