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

Phase 3TerminatedNCT04327505

Karolinska Institutet34 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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