HOT-COVID: Handling Oxygenation Targets in COVID-19

Sponsor
Aalborg University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04425031
Collaborator
Rigshospitalet, Denmark (Other), Copenhagen Trial Unit, Center for Clinical Intervention Research (Other)
780
10
2
42.2
78
1.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed 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)

Study Design

Study Type:
Interventional
Anticipated Enrollment :
780 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Prevention
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
Actual Study Start Date :
Aug 25, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Low oxygenation target

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

Drug: Oxygen
Oxygen administration to achieve a PaO2 of 8 kPa (60 mmHg) from ICU admission to ICU discharge
Other Names:
  • Inspired oxygen
  • Active Comparator: High oxygenation target

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

    Drug: Oxygen
    Oxygen administration to achieve a PaO2 of 12 kPa (90 mmHg) from ICU admission to ICU discharge
    Other Names:
  • Inspired oxygen
  • Outcome Measures

    Primary Outcome Measures

    1. Days alive without organ support [Within 90 days]

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

    Secondary Outcome Measures

    1. 90-days mortality [90 days]

      All-cause mortality 90 days after randomisation

    2. Days alive out of the hospital [Within 90 days]

      Days alive out of the hospital

    3. Number of patients with one or more serious adverse events [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

    4. 1-year mortality [1 year]

      All-cause mortality 1 year after randomisation

    5. Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview [1 year]

      EQ-5D-5L 1-year after randomisation

    6. Cognitive function 1-year after randomisation as assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score in selected sites [1 year]

      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.

    7. Carbon monoxide diffusion capacity [1 year]

      Carbon monoxide diffusion capacity (DLCO) 1 year after randomisation at selected sites.

    8. A health economic analysis [90 days]

      Cost-effectiveness versus cost-minimisation analyses after completion of the trial, based on the primary outcome.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dept. of Intensive Care, Aalborg University Hospital Aalborg Denmark 9000
    2 Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet Copenhagen Denmark 2100
    3 Dept. of Intensive Care, Herlev Hospital Herlev Denmark 2730
    4 Dept. of Intensive Care, Hillerød Hospital Hillerød Denmark 3400
    5 Dept. of Intensive Care, Kolding Hospital Kolding Denmark 6000
    6 Dept. of Intensive Care, Køge Hospital Køge Denmark 4600
    7 Randers Hospital Randers Denmark 8930
    8 Dept. of Intensive Care, Slagelse Hospital Slagelse Denmark 4200
    9 Oslo University Hospital Oslo Norway
    10 Universitätsspital Basel Basel Switzerland 4031

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Bodil Steen Rasmussen, MD, PhD, Aalborg University Hospital, Denmark
    • Study Chair: Bodil Steen Rasmussen, MD, PhD, Aalborg University Hospital, Denmark

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Bodil Steen Rasmussen, Clinical Professor, MD, PhD, Aalborg University Hospital
    ClinicalTrials.gov Identifier:
    NCT04425031
    Other Study ID Numbers:
    • AAUH-ICU-03
    • 2017-000632-34
    First Posted:
    Jun 11, 2020
    Last Update Posted:
    Nov 1, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bodil Steen Rasmussen, Clinical Professor, MD, PhD, Aalborg University Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 1, 2021