Handling Oxygenation Targets in the Intensive Care Unit

Overview

Handling oxygenation targets (HOT) is standard of care in the intensive care unit (ICU), however the quality and quantity of evidence is low and potential harm has been reported. The aim of the HOT-ICU trial is to assess the overall benefits and harms of two levels of oxygenation targets in adult critically ill patients with acute hypoxaemic respiratory failure in the ICU.

Full Title of Study: “Handling Oxygenation Targets in Adults With Acute Hypoxaemic Respiratory Failure in the Intensive Care Unit: A Randomised Clinical Trial of a Lower Versus a Higher Oxygenation Target”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: November 3, 2020

Detailed Description

Acutely ill adults with hypoxaemic respiratory failure admitted to the intensive care unit (ICU) are at risk of life-threatening hypoxia, and thus oxygen is administered. However, the evidence on the optimal level of oxygenation is of low quantity and quality with no firm evidence for benefit or harm. Importantly, liberal use of supplementary oxygen may increase the number of serious adverse events including death. The aim of the HOT-ICU trial is to assess the benefits and harms of two targets of partial pressure of oxygen in arterial blood (PaO2) in guiding the oxygen administration in acutely ill adults with hypoxaemic respiratory failure at ICU admission.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Low oxygenation target
    • Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg)
  • Active Comparator: High oxygenation target
    • Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg)

Clinical Trial Outcome Measures

Primary Measures

  • 90-days mortality
    • Time Frame: 90 days
    • Landmark mortality 90-days after randomisation

Secondary Measures

  • Days alive without organ support
    • Time Frame: Within 90 days
    • Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
  • Days alive out of the hospital
    • Time Frame: Within 90 days
    • Percentage of days alive out of the hospital
  • Number of patients with one or more serious adverse events
    • Time Frame: 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
    • Time Frame: 1 year
    • Landmark mortality 1 year after randomisation
  • Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites
    • Time Frame: 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
    • Time Frame: 1 year
    • RBANS score 1 year after randomisation at selected sites
  • Pulmonary function
    • Time Frame: 1 year
    • Bodyplethysmography and carbon monooxide diffusion capacity 1 year after randomisation at sellected sites
  • A health economic analysis
    • Time Frame: 90 days
    • The analytic details will be based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses)

Participating in This Clinical Trial

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 at least a FiO2 of 0.50 in a closed system including invasive or non-invasive ventilation or CPAP systems AND – Expected to receive supplemental oxygen for at least 24 hours in the ICU AND – Having an arterial line for PaO2 monitoring 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-ICU trial

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Aalborg University Hospital
  • Collaborator
    • Rigshospitalet, Denmark
  • Provider of Information About this Clinical Study
    • Principal Investigator: Bodil Steen Rasmussen, Clinical Professor, MD, PhD – Aalborg University Hospital
  • Overall Official(s)
    • Bodil Steen Rasmussen, MD, PhD, Principal Investigator, Aalborg University Hospital, Denmark
    • Anders Perner, MD, PhD, Study Chair, Rigshospitalet, Denmark

References

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.

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.

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.

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.

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.

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