Handling Oxygenation Targets in COVID-19

NCT04425031 | Completed Phase 4 DMC

• 2 other identifiers: AAUH-ICU-032017-000632-34
• Study Type: interventional
• Target: 726
• Locations: 3 countries
• Sites: 10

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.

Conditions

Hypoxemic Respiratory Failure; Oxygen Toxicity

Keywords

Oxygenation; Acute Respiratory Distress Syndrome; Mechanical ventilation; Critical illness; Critical care

Outcome Measures

Primary Outcomes (1)

• Days alive without organ support

  Days alive and free from mechanical ventilation, circulatory support and renal replacement therapy

  Within 90 days

Secondary Outcomes (8)

• 90-days mortality

  90 days

• Days alive out of the hospital

  Within 90 days

• Number of patients with one or more serious adverse events

  Until ICU discharge, maximum 90 days

• 1-year mortality

  1 year

• Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview

  1 year

Study Arms (2)

Low oxygenation target

EXPERIMENTAL

Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg)

Drug: Low oxygenation target

High oxygenation target

ACTIVE COMPARATOR

Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg)

Drug: High oxygenation target

Interventions

Low oxygenation target DRUG

Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge

Also known as: Inspired oxygen

Low oxygenation target

High oxygenation target DRUG

Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge

Also known as: Inspired oxygen

High oxygenation target

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aalborg University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator

Study Sites (10)

Dept. of Intensive Care, Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Intensive Care, Herlev Hospital

Herlev, 2730, Denmark

Location

Dept. of Intensive Care, Hillerød Hospital

Hillerød, 3400, Denmark

Location

Dept. of Intensive Care, Kolding Hospital

Kolding, 6000, Denmark

Location

Dept. of Intensive Care, Køge Hospital

Køge, 4600, Denmark

Location

Randers Hospital

Randers, 8930, Denmark

Location

Dept. of Intensive Care, Slagelse Hospital

Slagelse, 4200, Denmark

Location

Oslo University Hospital

Oslo, Norway

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Related Publications (8)

• 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.

  PMID: 30883686 BACKGROUND

• 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.

  PMID: 29708586 BACKGROUND

• 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.

  PMID: 31773728 BACKGROUND

• 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.

  PMID: 30527413 BACKGROUND

• 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.

  PMID: 32068884 BACKGROUND

• Nielsen 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.

  PMID: 38990335 RESULT

• Nielsen 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.

  PMID: 38501214 RESULT

• Nielsen 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.

  PMID: 39303806 DERIVED

Related Links

• Link to the HOT-COVID website

MeSH Terms

Conditions

Respiratory Insufficiency; Respiratory Distress Syndrome; Critical Illness

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bodil Steen Rasmussen, MD, PhD

  Aalborg University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

• Bodil Steen Rasmussen, MD, PhD

  Aalborg University Hospital, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor, MD, PhD

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 11, 2020
• Study Start: August 25, 2020
• Primary Completion: March 8, 2023
• Study Completion: March 8, 2024
• Last Updated: July 15, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available from June 2024 and for 10 years ahead.
• Access Criteria: Access Criteria: Managed by the Steering Committee of the HOT-COVID trial.

Locations

NO (1); CH (1); DK (8)