Handling Oxygenation Targets in the Intensive Care Unit

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hypoxemic Respiratory Failure, Oxygen Toxicity

Intervention / Treatment
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* Drug: Oxygen
* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low oxygenation target<br>Partial pressure of oxygen in arterial blood (PaO2) 8 kPa (60 mmHg) | Drug: Oxygen<br>* Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge<br>* Other names: Inspired oxygen;|
| Active Comparator: High oxygenation target<br>Partial pressure of oxygen in arterial blood (PaO2) 12 kPa (90 mmHg) | Drug: Oxygen<br>* Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge<br>* Other names: Inspired oxygen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-days mortality | Landmark mortality 90-days after randomisation | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive without organ support | Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy | Within 90 days | 
| Days alive out of the hospital | Percentage of days alive out of the hospital | Within 90 days | 
| 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 | 
| 1-year mortality | Landmark mortality 1 year after randomisation | 1 year | 
| Quality of life assessement using the EuroQual-5D-5L telephone interview in selcted sites | EQ-5D-5L 1-year after randomisation | 1 year | 
| 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 | 1 year | 
| Pulmonary function | Bodyplethysmography and carbon monooxide diffusion capacity 1 year after randomisation at sellected sites | 1 year | 
| A health economic analysis | The analytic details will be based on the result of the trial and specified (cost-effectiveness versus cost-minimisation analyses) | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxygenation, Acute Respiratory Distress Syndrome, Mechanical ventilation, Critical illness, Critical care