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Handling Oxygenation Targets in COVID-19 (HOT-COVID)

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ClinicalTrials.gov Identifier: NCT04425031
Recruitment Status : Not yet recruiting
First Posted : June 11, 2020
Last Update Posted : June 16, 2020
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
Information provided by (Responsible Party):
Bodil Steen Rasmussen, Aalborg University Hospital

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
Hypoxemic Respiratory Failure Oxygen Toxicity Drug: Oxygen 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)

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : August 1, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : March 1, 2024


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 Name: 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 Name: Inspired oxygen




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 90-days mortality [ Time Frame: 90 days ]
    All-cause mortality 90 days after randomisation

  2. Days alive out of the hospital [ Time Frame: Within 90 days ]
    Percentage of days alive out of the hospital

  3. 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

  4. 1-year mortality [ Time Frame: 1 year ]
    All-cause mortality 1 year after randomisation

  5. Quality of life assessement using the EuroQoL EQ-5D-5L telephone interview [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 year ]
    Carbon monoxide diffusion capacity (DLCO) 1 year after randomisation at selected sites.

  8. A health economic analysis [ Time Frame: 90 days ]
    Cost-effectiveness versus cost-minimisation analyses after completion of the trial, based on the primary outcome.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04425031


Contacts
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Contact: Bodil Steen Rasmussen, MD, PhD +4597661864 bodil.steen.rasmussen@rn.dk
Contact: Thomas Lass Klitgaard, MD +4597661870 tlk@rn.dk

Locations
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Denmark
Dept. of Intensive Care, Aalborg University Hospital
Aalborg, Denmark, 9000
Contact: Olav Lilleholt Schjørring, MD, PhD       o.schjorring@rn.dk   
Sponsors and Collaborators
Aalborg University Hospital
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
Investigators
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Principal Investigator: Bodil Steen Rasmussen, MD, PhD Aalborg University Hospital, Denmark
Study Chair: Bodil Steen Rasmussen, MD, PhD Aalborg University Hospital, Denmark
Additional Information:
Publications:

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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 ( EudraCT Number )
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All original records (incl. consent forms, electronic clinical report forms (eCRFs), and relevant correspondences) will be archived at trial sites for 15 years. The clean electronic trial database file will be delivered to the EudraCT Database and Zenodo data repository (https://zenodo.org/) and maintained for 15 years and anonymised if requested by the authorities.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Access Criteria:

Access Criteria:

Managed by the Steering Committee of the HOT-COVID trial.

URL: http://cric.nu/hot-covid

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bodil Steen Rasmussen, Aalborg University Hospital:
Oxygenation
Acute Respiratory Distress Syndrome
Mechanical ventilation
Critical illness
Critical care
Additional relevant MeSH terms:
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Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases