Clinical trial NCT04327505: Safety and Efficacy of Hyperbaric Oxygen for ARDS in Patients With COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: SARS (Severe Acute Respiratory Syndrome)
Cytokine Storm
ARDS, Human
COVID-19
Sars-CoV2
Acute Respiratory Failure
Keywords: COVID-19
Hyperbaric oxygen
ARDS
SARS-CoV-2
ICU admission
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska Trial Alliance
name: University of California, San Diego
name: Blekinge County Council Hospital
name: JK Biostatistics AB
name: The Swedish Research Council
name: University of Regensburg
First posted: 2020-03-31
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled, open label, multi-centre clinical trial
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: ICU admission
timeFrame: Through study completion 30 days
Secondary outcomes:
measure: 30-day mortality
timeFrame: Through study completion 30 days
measure: Time-to-intubation
timeFrame: Through study completion 30 days
measure: Time-to-ICU
timeFrame: Through study completion 30 days
measure: Inflammatory response
timeFrame: Through study completion 30 days
measure: Overall survival
timeFrame: Through study completion 30 days
Other outcomes:
measure: Hospital mortality
timeFrame: Through study completion 30 days
measure: ICU mortality
timeFrame: From ICU admission to study completion 30 days
measure: Time in Invasive Ventilation
timeFrame: From ICU admission to study completion 30 days
measure: NEWS
timeFrame: Through study completion 30 days
measure: PaO2/FiO2 (PFI)
timeFrame: Through study completion 30 days
measure: HBO Compliance
timeFrame: Day 1 to day 7
measure: Hospital discharge
timeFrame: Through study completion 30 days
measure: Oxygen dose
timeFrame: Through study completion 30 days
measure: HBO dose
timeFrame: Day 1 to day 7
measure: Micro RNA
timeFrame: Through study completion 30 days
measure: Hypoxic response
timeFrame: Through study completion 30 days
measure: Immunological response
timeFrame: Through study completion 30 days
measure: Multi organ dysfunction
timeFrame: Through study completion 30 days
measure: Viral load
timeFrame: Through study completion 30 days
measure: Secondary infections
timeFrame: Through study completion 30 days
measure: Pulmonary embolism
timeFrame: Through study completion 30 days
measure: Pulmonary CT
timeFrame: Through study completion 30 days
measure: Chest X-ray
timeFrame: Through study completion 30 days
measure: Lung ultrasound
timeFrame: Through study completion 30 days
Locations:
city: Regensburg
country: Germany
facility: Krankenhaus St. Joesf
city: Karlskrona
country: Sweden
facility: Blekingesjukhuset
state: Blekinge
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska Institutet
name: Anders Kjellberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Peter Lindholm, MD, PhD
role: STUDY_CHAIR
affiliation: Karolinska Institutet
name: Kenny Rodriguez-Wallberg, MD, PhD
role: STUDY_CHAIR
References:
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citation: Oscarsson N, Muller B, Rosen A, Lodding P, Molne J, Giglio D, Hjelle KM, Vaagbo G, Hyldegaard O, Vangedal M, Salling L, Kjellberg A, Lind F, Ettala O, Arola O, Seeman-Lodding H. Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial. Lancet Oncol. 2019 Nov;20(11):1602-1614. doi: 10.1016/S1470-2045(19)30494-2. Epub 2019 Sep 16.
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citation: Gorenstein SA, Castellano ML, Slone ES, Gillette B, Liu H, Alsamarraie C, Jacobson AM, Wall SP, Adhikari S, Swartz JL, McMullen JJS, Osorio M, Koziatek CA, Lee DC. Hyperbaric oxygen therapy for COVID-19 patients with respiratory distress: treated cases versus propensity-matched controls. Undersea Hyperb Med. 2020 Third Quarter;47(3):405-413. doi: 10.22462/01.03.2020.1.
citation: Kjellberg A, De Maio A, Lindholm P. Can hyperbaric oxygen safely serve as an anti-inflammatory treatment for COVID-19? Med Hypotheses. 2020 Nov;144:110224. doi: 10.1016/j.mehy.2020.110224. Epub 2020 Aug 30.
citation: Kjellberg A, Douglas J, Pawlik MT, Kraus M, Oscarsson N, Zheng X, Bergman P, Franberg O, Kowalski JH, Nyren SP, Silvanius M, Skold M, Catrina SB, Rodriguez-Wallberg KA, Lindholm P. Randomised, 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. BMJ Open. 2021 Jul 5;11(7):e046738. doi: 10.1136/bmjopen-2020-046738.