Futility, change of disease due to virus mutations and/or vaccination

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.

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

Inclusion criteria:

1. Aged 18-90 years

2. PaO2/FiO2 (PFI) below 200 mmHg (26.7 kPa)

3. Suspected or verified SARS-CoV-2 infection

4. 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

5. Documented informed consent according to ICH-GCP and national regulations

Exclusion Criteria:

1. ARDS/pneumonia caused by other viral infections (positive for other virus)
2. ARDS/pneumonia caused by other non-viral infections or trauma
3. Known pregnancy or positive pregnancy test in women of childbearing age
4. Patients with previous lung fibrosis more than 10%
5. CT- or Spirometry-verified severe COPD with Emphysema
6. Contraindication for HBO according to local guidelines
7. 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)
8. Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
9. Prisoner (Exclusion criteria according to IRB at UCSD)

Adults, all genders

The full study protocol, statistical plan and consent form will be publicly available when results are published. Data will be available on patient level; data will be pseudonymized. The full dataset and statistical code will be available upon request.

Starting after publication and for 36 months

A full description of the intended use of the data must be sent to the corresponding author for review and approval. Participant consent for data sharing is conditioned and new ethics approval may be required.