Hyperbaric Versus Normobaric Oxygen Therapy for COVID-19 Patients

• ClinicalTrials.gov Identifier: NCT04500626
• Recruitment Status: Recruiting
• First Posted: August 5, 2020
• Last Update Posted: November 1, 2021
• Sponsor: Ottawa Hospital Research Institute
• Collaborator: Climate Foundation
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Tracking Information

• First Submitted Date: July 31, 2020
• First Posted Date: August 5, 2020
• Last Update Posted Date: November 1, 2021
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2020)

7-level COVID Ordinal Outcome Scale [ Time Frame: Measured on Day 7 ]

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.

Original Primary Outcome Measures (submitted: August 4, 2020)

7-level COVID ordinal outcome scale [ Time Frame: Measured on Day 7 ]

7-level scale based on patient's current status and need for oxygenation, also ability to resume normal activities (at higher levels)

Current Secondary Outcome Measures (submitted: August 10, 2020)

• Length of hospital stay [ Time Frame: Duration of study (to Day 28) ]
  Measured in days
• Days with oxygen supplementation [ Time Frame: Duration of study (to Day 28) ]
  Number of days with oxygen supplementation
• Daily oxygen flow values required to obtain saturation values ≥90%, [ Time Frame: Duration of study (to Day 28) ]
  Measured in L/min
• ICU admission [ Time Frame: Duration of study (to Day 28) ]
  Yes/No
• ICU length of stay [ Time Frame: Duration of study (to Day 28) ]
  Measured in days, if applicable
• Days on invasive mechanical ventilation or high flow oxygenation [ Time Frame: Duration of study (to Day 28) ]
  Number of days on ventilator
• Major arterial and venous thrombotic events [ Time Frame: Duration of study (to Day 28) ]
  e.g. stroke, pulmonary embolism, deep vein thrombosis
• Sleep quality [ Time Frame: Duration of study (to Day 28) ]
  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
• Fatigue [ Time Frame: Duration of study (to Day 28) ]
  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.
• 7-level COVID Ordinal Outcome Scale [ Time Frame: Measured on Day 28 ]
  Same scale as the primary outcome; different timing as a secondary outcome. Range is 1-7. Higher number indicates better clinical outcome.
• Mortality [ Time Frame: Duration of study (to Day 28) ]
  Number of deaths
• Incidence of any adverse events related to HBOT [ Time Frame: Duration of study (to Day 28) ]
  Number of adverse events

Original Secondary Outcome Measures (submitted: August 4, 2020)

• Length of hospital stay [ Time Frame: Duration of study (to Day 28) ]
  Measured in days
• Days with oxygen supplementation [ Time Frame: Duration of study (to Day 28) ]
  Number of days with oxygen supplementation
• Daily oxygen flow values required to obtain saturation values ≥90%, [ Time Frame: Duration of study (to Day 28) ]
  Measured in L/min
• ICU admission [ Time Frame: Duration of study (to Day 28) ]
  Yes/No
• ICU length of stay [ Time Frame: Duration of study (to Day 28) ]
  Measured in days, if applicable
• Days on invasive mechanical ventilation or high flow oxygenation [ Time Frame: Duration of study (to Day 28) ]
  Number of days on ventilator
• Major arterial and venous thrombotic events [ Time Frame: Duration of study (to Day 28) ]
  e.g. stroke, pulmonary embolism, deep vein thrombosis
• Sleep quality [ Time Frame: Duration of study (to Day 28) ]
  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
• Fatigue [ Time Frame: Duration of study (to Day 28) ]
  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.
• 7-level COVID ordinal outcome scale [ Time Frame: Measured on Day 28 ]
  Same scale as the primary outcome; different timing as a secondary outcome
• Mortality [ Time Frame: Duration of study (to Day 28) ]
  Number of deaths
• Safety events [ Time Frame: Duration of study (to Day 28) ]
  Incidence of any adverse events related to HBOT

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Covid19

Intervention

Drug: Oxygen

Hyperbaric oxygen therapy delivered in a monoplace or multi-place chamber. Supervised by a hyperbaric oxygen therapy physician and a chamber operator.

Study Arms

• Experimental: HBOT
  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.
  Intervention: Drug: Oxygen
• No Intervention: Control
  These patients will receive usual treatment for COVID-19, including oxygenation at normal atmospheric pressure (normobaric oxygenation).

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 4, 2020): 234
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2022
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sylvain Boet, MD, PhD; 613-737-8899 ext 78187; sboet@toh.ca

Contact: Joseph Burns, MSc; 613-798-5555 ext 14775; josburns@ohri.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT04500626
• Other Study ID Numbers: OHRI-HBOT-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ottawa Hospital Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Ottawa Hospital Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Climate Foundation

Investigators

• Principal Investigator: Sylvain Boet, MD, PhD; The Ottawa Hospital

• PRS Account: Ottawa Hospital Research Institute
• Verification Date: October 2021