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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2020-001349-37
    Sponsor's Protocol Code Number:COVID-19-HBO
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-04-24
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSweden - MPA
    A.2EudraCT number2020-001349-37
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Is Hyperbaric oxygen Safe and Effective for preventing ICU admission, worsening of disease and death in severe cases of COVID-19? A scientific study conducted in several hospitals world wide.
    A.3.2Name or abbreviated title of the trial where available
    Safety and Efficacy of Hyperbaric oxygen for ARDS in patients with COVID-19
    A.4.1Sponsor's protocol code numberCOVID-19-HBO
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04327505
    A.5.4Other Identifiers
    Name:Karolinska InstitutetNumber:K-1199/2020
    Name:Karolinska University HospitalNumber:K-2020/2611
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKarolinska Institutet
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSwedish Research Council
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportKarolinska Institutet
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportUniversity of California San Diego
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKarolinska Institutet
    B.5.2Functional name of contact pointAnders Kjellberg
    B.5.3 Address:
    B.5.3.1Street AddressBiomedicum, Solnavägen 9
    B.5.3.2Town/ citySolna
    B.5.3.3Post code171 65
    B.5.3.4CountrySweden
    B.5.4Telephone number+46760657355
    B.5.6E-mailanders.kjellberg@ki.se
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Conoxia 100%, Medicinal gas, cryogenic
    D.2.1.1.2Name of the Marketing Authorisation holderAGA
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameOxygen 100%
    D.3.4Pharmaceutical form Medicinal gas, cryogenic
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOXYGEN
    D.3.9.2Current sponsor codeOxygen
    D.3.9.4EV Substance CodeSUB14733MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeMedicinal gas
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Conoxia 100%, Medicinal gas, compressed
    D.2.1.1.2Name of the Marketing Authorisation holderLinde Gas
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameOxygen 100%
    D.3.4Pharmaceutical form Medicinal gas, compressed
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOXYGEN
    D.3.9.2Current sponsor codeOxygen
    D.3.9.4EV Substance CodeSUB14733MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeMedicinal gas
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    COVID-19 (SARS-CoV-2)
    E.1.1.1Medical condition in easily understood language
    COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate if HBO reduce the number of ICU admissions compared to Best practice for COVID-19
    E.2.2Secondary objectives of the trial
    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.
    E.2.3Trial contains a sub-study No
    E.3Principal 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
    E.4Principal 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 pregnabest practicency 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 fullfill 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)
    E.5 End points
    E.5.1Primary end point(s)
    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 Hypercapnea or increased work of breathing not responding to increased oxygen despite maximum standard of care available outside ICU
    iv) Hemodynamic instability or multi organ failiure with maximum standard of care availible outside ICU
    E.5.1.1Timepoint(s) of evaluation of this end point
    30 days after randomization
    E.5.2Secondary end point(s)
    Main Secondary Efficacy Endpoints
    I. Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30.
    II. Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30
    III. 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.
    IV. Mean change in inflammatory response from day 1 to day 30.
    a. White cell count + differentiation
    b. Procalcitonin
    c. C-Reactive protein
    d. Cytokines (IL-6) (if available at local laboratory)
    e. Ferritin
    f. D-Dimer
    g. LDH
    VI. Overall Survival

    Other Efficacy Endpoints
    I. Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.
    II. Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30.
    III. Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.
    IV. Mean daily NEWS from day 1 to day 30.
    V. Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.
    VI. HBO Compliance
    a. Proportion of HBO treatments given vs planned.
    b. Proportion of subjects with HBO treatment administered within 24h after enrollment.
    VII. Time-to-discharge from hospital.

    Exploratory/Descriptive Endpoints
    I. 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.
    II. Median number of HBO treatments and dose of HBO given, from day 1 to day 7.
    III. Change in expression of Micro RNA in plasma from day 1 to day 30.
    IV. Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) from day 1 to day 30 immunological response (20 subjects) from day 1 to day 30 in the following.
    a. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα)
    b. Lymphocyte profile
    c. Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio
    d. FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα),
    e. T-reg cells (CD3+/CD4+/CD25+/CD127+)
    f. Monocyte proliferation markers, Ex vivo monocyte function
    V. Mean change in routine biomarkers for organ dysfunction, from day 1 to day 30.
    VI. Viral load, from day 1 to day 30.
    VII. Number of secondary infections, number of events and patients from day 1 to day 30.
    VIII. Diagnosed PE needing treatment, number of events and patients from day 1 to day 30.
    IX. Changes on Pulmonary CT from day 1 to day 30.
    X. Changes on Chest X-ray, from day 1 to day 30.
    XI. Changes in Lung ultrasound,from day 1 to day 30.

    Safety Endpoints
    I. Number of subjects, proportion of subjects and number of events of AE.
    II. Number of subjects, proportion of subjects and number of events of SAE
    III. Number of subjects, proportion of subjects and number of events of SADR.
    IV. Mean change in PaO2/FiO2 before and after HBO compared to mean variance in PaO2/FiO2 in control group during day 1 to day 7.
    V. Mean change in NEWS before and after HBO compared to mean change in daily NEWS in control group during day 1-day 7.
    VI. Number of negative events in staff associated with treatment of subject, (e.g. contact with aerosol from subject), number of events from day 1 to day 30 or last day in hospital if subject is discharged earlier, or at withdrawal.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoints as specified in respective endpoint
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Best practice
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Germany
    Netherlands
    Spain
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 130
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    A patient group with high mortality and no effective cure
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 200
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The participants will be treated according to routine clinical praxis.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-05-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-29
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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