Safety and Efficacy of Hyperbaric Oxygen for ARDS in Patients With COVID-19

Study Overview
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Brief Summary
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COVID-19 may cause severe pneumonitis that require ventilatory support in some patients, the ICU mortality is as high as 62%. Hospitals do not have enough ICU beds to handle the demand and to date there is no effective cure. We explore a treatment administered in a randomized clinical trial that could prevent ICU admission and reduce mortality. The overall hypothesis to be evaluated is that HBO reduce mortality, increase hypoxia tolerance and prevent organ failure in patients with COVID19 pneumonitis by attenuating the inflammatory response.

Detailed Description
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Main objective: To evaluate if HBO reduce the number of ICU admissions compared to Best practice for COVID-19 Secondary objectives: Main secondary objectives: To evaluate if HBO: reduces mortality in severe cases of COVID-19. reduces morbidity associated with COVID-19. reduce the load on ICU resources in COVID-19. mitigate the inflammatory reaction in COVID-19. Other secondary objectives (in selection): To evaluate if HBO is safe for SARS-CoV-2 positive patients and staff. Study design: Randomized, controlled, phase II, open label, multicentre Study population: Adult patients with SARS-CoV-2 infection, with at least two risk factor for increased mortality, likely to develop ARDS criteria and need intubation within 7 days of admission to hospital. Number of subjects: 200 (20+180) Investigational product: Hyperbaric oxygen (HBO) compared with best practice treatment HBO: HBO 1.6-2.4 ATA for 30-60 min, maximum 5 treatments first 7 days Control: Best practice treatment for COVID-19

Official Title
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A Randomized, Controlled, Open Label, Multicentre Clinical Trial to Explore Safety and Efficacy of Hyperbaric Oxygen for Preventing ICU Admission, Morbidity and Mortality in Adult Patients With COVID-19

Conditions
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SARS (Severe Acute Respiratory Syndrome), Cytokine Storm, ARDS, Human, COVID-19, Sars-CoV2, Acute Respiratory Failure

Intervention / Treatment
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* Drug: Hyperbaric oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Aged 18-90 years PaO2/FiO2 (PFI) below 200 mmHg (26.7 kPa) Suspected or verified SARS-CoV-2 infection At least two risk factors for increased morbidity/mortality Age above 50 years Hypertension Cardiovascular disease Diabetes or pre-diabetes Active or cured cancer Asthma/COPD Smoking D-Dimer > 1.0 mg/L Auto-immune disease Documented informed consent according to ICH-GCP and national regulations Exclusion Criteria: ARDS/pneumonia caused by other viral infections (positive for other virus) ARDS/pneumonia caused by other non-viral infections or trauma Known pregnancy or positive pregnancy test in women of childbearing age Patients with previous lung fibrosis more than 10% CT- or Spirometry-verified severe COPD with Emphysema Contraindication for HBO according to local guidelines Not likely to need ICU admission < 7 days of screening (Subjective criteria that may exclude any patients that fulfil the other inclusion criteria but where the treating physician suspect a spontaneous recovery) Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation Prisoner (Exclusion criteria according to IRB at UCSD)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Interventional Model Description: Randomized controlled, open label, multi-centre clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric oxygen<br>Hyperbaric oxygen 1,6-2.4 Bar for 30-60 minutes (compression/decompression time, according to local routines) in addition to best practice | Drug: Hyperbaric oxygen<br>* 1.6- 2.4 ATA, 30-60 min (excluding compression/recompression)<br>* Other names: HBO;|
| No Intervention: Control<br>Best practice | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU admission | The proportion of subjects admitted to ICU from day 1 to day 30, based on at least one of the following criteria: i) Rapid progression over hours ii) Lack of improvement on high flow oxygen >40L/min or non invasive ventilation with fraction of inspired oxygen (FiO2) > 0.6 iii) Evolving Hypercapnia or increased work of breathing not responding to increased oxygen despite maximum standard of care available outside ICU iv) Hemodynamic instability or multi organ failure with maximum standard of care available outside ICU | Through study completion 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day mortality | Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30. | Through study completion 30 days | 
| Time-to-intubation | Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30 | Through study completion 30 days | 
| Time-to-ICU | Time-to-ICU, i.e. cumulative ICU free days, derived as the number of days from day 1 to ICU, where all ICU free subjects are censored at day 30. | Through study completion 30 days | 
| Inflammatory response | Mean change in inflammatory response from day 1 to day 30. White cell count + differentiation Procalcitonin C-Reactive protein Cytokines (IL-6) (if available at local laboratory) Ferritin D-Dimer LDH | Through study completion 30 days | 
| Overall survival | Overall survival (Kaplan-Meier) | Through study completion 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Hyperbaric oxygen, ARDS, SARS-CoV-2, ICU admission