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Trial record 1 of 2 for:    hbo | COVID
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Safety and Efficacy of Hyperbaric Oxygen for ARDS in Patients With COVID-19 (COVID-19-HBO)

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ClinicalTrials.gov Identifier: NCT04327505
Recruitment Status : Recruiting
First Posted : March 31, 2020
Last Update Posted : May 20, 2020
Sponsor:
Collaborators:
Karolinska Trial Alliance
University of California, San Diego
Blekinge County Council Hospital
JK Biostatistics AB
The Swedish Research Council
Information provided by (Responsible Party):
Anders Kjellberg, MD, Karolinska Institutet

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 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
Estimated Study Start Date : May 22, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022


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 Name: HBO

No Intervention: Control
Best practice



Primary Outcome Measures :
  1. ICU admission [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through study completion 30 days ]

    Mean change in inflammatory response from day 1 to day 30.

    1. White cell count + differentiation
    2. Procalcitonin
    3. C-Reactive protein
    4. Cytokines (IL-6) (if available at local laboratory)
    5. Ferritin
    6. D-Dimer
    7. LDH

  5. Overall survival [ Time Frame: Through study completion 30 days ]
    Overall survival (Kaplan-Meier)


Other Outcome Measures:
  1. Hospital mortality [ Time Frame: Through study completion 30 days ]
    Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.

  2. ICU mortality [ Time Frame: 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 [ Time Frame: From ICU admission to study completion 30 days ]
    Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.

  4. NEWS [ Time Frame: Through study completion 30 days ]
    Mean daily NEWS from day 1 to day 30.

  5. PaO2/FiO2 (PFI) [ Time Frame: Through study completion 30 days ]
    Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.

  6. HBO Compliance [ Time Frame: Day 1 to day 7 ]
    1. Proportion of HBO treatments given vs planned.
    2. Proportion of subjects with HBO treatment administered within 24h after enrolment.

  7. Hospital discharge [ Time Frame: Through study completion 30 days ]
    Time-to-discharge from hospital

  8. Oxygen dose [ Time Frame: 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 [ Time Frame: Day 1 to day 7 ]
    Median number of HBO treatments and dose of HBO given, from day 1 to day 7

  10. Micro RNA [ Time Frame: Through study completion 30 days ]
    Change in expression of Micro RNA in plasma from day 1 to day 30

  11. Hypoxic response [ Time Frame: 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 [ Time Frame: Through study completion 30 days ]

    Immunological response (20 subjects) from day 1 to day 30 in the following.

    1. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα)
    2. Lymphocyte profile
    3. Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio
    4. FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα),
    5. T-reg cells (CD3+/CD4+/CD25+/CD127+)
    6. Monocyte proliferation markers, Ex vivo monocyte function

  13. Multi organ dysfunction [ Time Frame: Through study completion 30 days ]
    Mean change in routine biomarkers for organ dysfunction, from day 1to day 30.

  14. Viral load [ Time Frame: Through study completion 30 days ]
    Viral load, review of records from day 1 to day 30.

  15. Secondary infections [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Through study completion 30 days ]
    Changes on Pulmonary CT, review of records from day 1 to day 30.

  18. Chest X-ray [ Time Frame: Through study completion 30 days ]
    Changes on Chest X-ray, review of records from day 1 to day 30.

  19. Lung ultrasound [ Time Frame: Through study completion 30 days ]
    Changes in Lung ultrasound, review of records from day 1 to day 30.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Adults, all genders
Accepts Healthy Volunteers:   No
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
    • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04327505


Contacts
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Contact: Anders Kjellberg, MD +46812375212 anders.kjellberg@ki.se
Contact: Peter Lindholm, MD, PhD +16508230735 peter.lindholm@health.ucsd.edu

Locations
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Germany
Bergmannsheil und Kinderklinik Buer GmbH Not yet recruiting
Gelsenkirchen, Germany, 45894
Contact: Georg Rinneberg    +4916093954430    georg.rinneberg@bergmannsheil-buer.de   
Principal Investigator: Michael Kraus, MD         
Krankenhaus St. Joesf Not yet recruiting
Regensburg, Germany, 93053
Contact: Michael Pawlik, MD, PhD    +499417823610    mpawlik@caritasstjosef.de   
Principal Investigator: Michael Pawlik, MD, PhD         
Sweden
Blekingesjukhuset Recruiting
Karlskrona, Blekinge, Sweden
Contact: Johan Douglas, MD    +46708123223    j@douglas.nu   
Principal Investigator: Johan Douglas, MD         
Sponsors and Collaborators
Karolinska Institutet
Karolinska Trial Alliance
University of California, San Diego
Blekinge County Council Hospital
JK Biostatistics AB
The Swedish Research Council
Investigators
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Principal Investigator: Anders Kjellberg, MD Karolinska Institutet
Study Chair: Peter Lindholm, MD, PhD Karolinska Institutet
Study Chair: Kenny Rodriguez-Wallberg, MD, PhD Karolinska Institutet

Additional Information:
Publications:
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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 ( EudraCT Number )
K-1199/2020 ( Registry Identifier: Karolinska Institutet )
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, Karolinska Institutet:
COVID-19
Hyperbaric oxygen
ARDS
SARS-CoV-2
ICU admission
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Respiratory Insufficiency
Respiratory Distress Syndrome, Adult
Respiration Disorders
Respiratory Tract Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Lung Diseases