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

Sponsor
Karolinska Institutet (Other)
Overall Status
Recruiting
CT.gov ID
NCT04327505
Collaborator
Karolinska Trial Alliance (Other), University of California, San Diego (Other), Blekinge County Council Hospital (Other), JK Biostatistics AB (Other), The Swedish Research Council (Other), University of Regensburg (Other)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Hyperbaric oxygen
Phase 2/Phase 3

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized controlled, open label, multi-centre clinical trialRandomized controlled, open label, multi-centre clinical trial
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 3, 2020
Anticipated Primary Completion Date :
Sep 30, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Hyperbaric oxygen

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
1.6- 2.4 ATA, 30-60 min (excluding compression/recompression)
Other Names:
  • HBO
  • No Intervention: Control

    Best practice

    Outcome Measures

    Primary Outcome Measures

    1. ICU admission [Through study completion 30 days]

      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

    Secondary Outcome Measures

    1. 30-day mortality [Through study completion 30 days]

      Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30.

    2. Time-to-intubation [Through study completion 30 days]

      Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30

    3. Time-to-ICU [Through study completion 30 days]

      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.

    4. Inflammatory response [Through study completion 30 days]

      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

    5. Overall survival [Through study completion 30 days]

      Overall survival (Kaplan-Meier)

    Other Outcome Measures

    1. Hospital mortality [Through study completion 30 days]

      Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.

    2. ICU mortality [From ICU admission to study completion 30 days]

      Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30.

    3. Time in Invasive Ventilation [From ICU admission to study completion 30 days]

      Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.

    4. NEWS [Through study completion 30 days]

      Mean daily NEWS from day 1 to day 30.

    5. PaO2/FiO2 (PFI) [Through study completion 30 days]

      Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.

    6. HBO Compliance [Day 1 to day 7]

      Proportion of HBO treatments given vs planned. Proportion of subjects with HBO treatment administered within 24h after enrolment.

    7. Hospital discharge [Through study completion 30 days]

      Time-to-discharge from hospital

    8. Oxygen dose [Through study completion 30 days]

      Mean oxygen dose per day including HBO and cumulative pulmonary oxygen toxicity expressed as Units of oxygen pulmonary toxicity dose (UPTD) and Cumulative pulmonary toxicity dose (CPTD) from day 1 to day 30.

    9. HBO dose [Day 1 to day 7]

      Median number of HBO treatments and dose of HBO given, from day 1 to day 7

    10. Micro RNA [Through study completion 30 days]

      Change in expression of Micro RNA in plasma from day 1 to day 30

    11. Hypoxic response [Through study completion 30 days]

      Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) (20 Subjects) from day 1 to day 30

    12. Immunological response [Through study completion 30 days]

      Immunological response (20 subjects) from day 1 to day 30 in the following. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα) Lymphocyte profile Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα), T-reg cells (CD3+/CD4+/CD25+/CD127+) Monocyte proliferation markers, Ex vivo monocyte function

    13. Multi organ dysfunction [Through study completion 30 days]

      Mean change in routine biomarkers for organ dysfunction, from day 1to day 30.

    14. Viral load [Through study completion 30 days]

      Viral load, review of records from day 1 to day 30.

    15. Secondary infections [Through study completion 30 days]

      Number of secondary infections, review of records, number of events and patients from day 1 to day 30.

    16. Pulmonary embolism [Through study completion 30 days]

      Diagnosed PE needing treatment, review of records, number of events and patients from day 1 to day 30.

    17. Pulmonary CT [Through study completion 30 days]

      Changes on Pulmonary CT, review of records from day 1 to day 30.

    18. Chest X-ray [Through study completion 30 days]

      Changes on Chest X-ray, review of records from day 1 to day 30.

    19. Lung ultrasound [Through study completion 30 days]

      Changes in Lung ultrasound, review of records from day 1 to day 30.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Krankenhaus St. Joesf Regensburg Germany 93053
    2 Blekingesjukhuset Karlskrona Blekinge Sweden
    3 Sahlgrenska University hospital, Östra sjukhuset Gothenburg Sweden 416 50
    4 Karolinska University Hospital Stockholm Sweden 171 76

    Sponsors and Collaborators

    • Karolinska Institutet
    • Karolinska Trial Alliance
    • University of California, San Diego
    • Blekinge County Council Hospital
    • JK Biostatistics AB
    • The Swedish Research Council
    • University of Regensburg

    Investigators

    • Principal Investigator: Anders Kjellberg, MD, Karolinska Institutet
    • Study Chair: Peter Lindholm, MD, PhD, Karolinska Institutet
    • Study Chair: Kenny Rodriguez-Wallberg, MD, PhD, Karolinska Institutet

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Anders Kjellberg, MD, ICU Consultant/PhD student, Karolinska Institutet
    ClinicalTrials.gov Identifier:
    NCT04327505
    Other Study ID Numbers:
    • COVID-19-HBO
    • 2020-001349-37
    • K-1199/2020
    First Posted:
    Mar 31, 2020
    Last Update Posted:
    Aug 16, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Anders Kjellberg, MD, ICU Consultant/PhD student, Karolinska Institutet
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 16, 2022