Hyperbaric Versus Normobaric Oxygen Therapy for COVID-19 Patients

Study Overview
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Brief Summary
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At least 1 in 6 COVID-19 patients admitted to hospital to receive extra oxygen will die of complications. In patients with COVID-19, invasive treatment such as mechanical ventilation (e.g. breathing with a machine) is associated with a 50% increased risk of death. Invasive treatments use a lot of healthcare resources in intensive care units and may lead to further deaths if patients do not have access to care. The investigators aim to improve outcomes for COVID-19 patients by implementing hyperbaric oxygen therapy (HBOT). HBOT allows patients to breathe 100% oxygen in a special chamber at a pressure higher than sea level. It is approved by Health Canada for 14 conditions. HBOT is safe when administered by experienced teams. There are two main causes of death in severe COVID-19 respiratory infections: (i) a decreased diffusion of oxygen from the lungs to the blood and (ii) an increased inflammatory response (also called a cytokine storm). HBOT leads to increased oxygen level in blood, has strong anti-inflammatory effects, and may destroy the virus responsible for COVID-19 disease. The initial experience with HBOT and COVID-19 from China, France and the United States is promising in that it prevents further worsening of the condition and need for intensive care. The investigators propose to test the effectiveness of HBOT for COVID-19 patients who are admitted to hospital to receive extra oxygen. Using the most rigorous and innovative research methods, this Canadian-led international study will operate at 5 centers across 3 countries (Canada: Ottawa, Toronto, Edmonton; Switzerland: Geneva; UK: Rugby/London). The investigators anticipate that when treated by HBOT, COVID-19 patients needing extra oxygen to breathe will see significant health improvements as well as a decrease in complications, inflammation in the blood, need for invasive care, death, and cost of care.

Official Title
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Multicentre Randomized Controlled Trial of Hyperbaric Versus Normobaric Oxygen Therapy for COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Drug: Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female patients Age ≥18 years Confirmed COVID-19 positive by RT-PCR or another validated method Diagnosed with pneumonia requiring 21%<FIO2≤100% to maintain saturation by pulse oximetry (SpO2) ≥90% Able and willing to comply with study procedures and follow-up examinations contained within the written consent form Exclusion Criteria: Patient clinical status felt to be incompatible with HBOT, e.g. respiratory failure requiring mechanical ventilation Pregnancy, determined by a serum or urine test Hemodynamic instability requiring vasopressors Inability to maintain a sitting position during treatment Inability to effectively understand and communicate with the hyperbaric operator, or to give consent Inability to spontaneously equalize ears and refusal of myringotomies Contraindications to HBOT (e.g. pneumothorax)

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBOT<br>These patients will receive hyperbaric oxygen therapy (HBOT) in addition to usual treatment for COVID-19. HBOT sessions will be 75 minutes in length at a pressure of 2.0 ATA. | Drug: Oxygen<br>* Hyperbaric oxygen therapy delivered in a monoplace or multi-place chamber. Supervised by a hyperbaric oxygen therapy physician and a chamber operator.<br>|
| No Intervention: Control<br>These patients will receive usual treatment for COVID-19, including oxygenation at normal atmospheric pressure (normobaric oxygenation). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-level COVID Ordinal Outcome Scale | 7-level scale based on patient's current status and need for oxygenation, also ability to resume normal activities (at higher levels). Range is 1-7. Higher number indicates better clinical outcome. | Measured on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Measured in days | Duration of study (to Day 28) | 
| Days with oxygen supplementation | Number of days with oxygen supplementation | Duration of study (to Day 28) | 
| Daily oxygen flow values required to obtain saturation values ≥90%, | Measured in L/min | Duration of study (to Day 28) | 
| ICU admission | Yes/No | Duration of study (to Day 28) | 
| ICU length of stay | Measured in days, if applicable | Duration of study (to Day 28) | 
| Days on invasive mechanical ventilation or high flow oxygenation | Number of days on ventilator | Duration of study (to Day 28) | 
| Major arterial and venous thrombotic events | e.g. stroke, pulmonary embolism, deep vein thrombosis | Duration of study (to Day 28) | 
| Sleep quality | Sleep Quality Scale, measured from 0 to 10. Higher number indicates worse sleep quality: 0 = best possible sleep, 10 = worst possible sleep. Capelleri et. al; Health and Quality of Life Outcomes 2009: 7:54 | Duration of study (to Day 28) | 
| Fatigue | Single-Item Fatigue Report Mark, measured from 1 to 10. Higher number indicates worse fatigue: 1 = not at all, 10 = extremely. van Hooff et al; J Occup Health 2007; 49:224-234. | Duration of study (to Day 28) | 
| 7-level COVID Ordinal Outcome Scale | Same scale as the primary outcome; different timing as a secondary outcome. Range is 1-7. Higher number indicates better clinical outcome. | Measured on Day 28 | 
| Mortality | Number of deaths | Duration of study (to Day 28) | 
| Incidence of any adverse events related to HBOT | Number of adverse events | Duration of study (to Day 28) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperbaric oxygen therapy