NCT04327505

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2020

Geographic Reach
2 countries

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 25, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 31, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

June 3, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2022

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2022

Completed
Last Updated

January 9, 2023

Status Verified

January 1, 2023

Enrollment Period

2.1 years

First QC Date

March 25, 2020

Last Update Submit

January 5, 2023

Conditions

SARS (Severe Acute Respiratory Syndrome)Cytokine StormARDS, HumanCOVID-19Sars-CoV2Acute Respiratory Failure

Keywords

COVID-19Hyperbaric oxygenARDSSARS-CoV-2ICU admission

Outcome Measures

Primary Outcomes (1)

  • 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

    Through study completion 30 days

Secondary Outcomes (5)

  • 30-day mortality

    Through study completion 30 days

  • Time-to-intubation

    Through study completion 30 days

  • Time-to-ICU

    Through study completion 30 days

  • Inflammatory response

    Through study completion 30 days

  • Overall survival

    Through study completion 30 days

Other Outcomes (19)

  • Hospital mortality

    Through study completion 30 days

  • ICU mortality

    From ICU admission to study completion 30 days

  • Time in Invasive Ventilation

    From ICU admission to study completion 30 days

  • +16 more other outcomes

Study Arms (2)

Hyperbaric oxygen

EXPERIMENTAL

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

Control

NO INTERVENTION

Best practice

Interventions

Hyperbaric oxygenDRUG

1.6- 2.4 ATA, 30-60 min (excluding compression/recompression)

Also known as: HBO
Hyperbaric oxygen

Eligibility Criteria

Age18 Years - 90 Years
Sexall(Gender-based eligibility)
Gender Eligibility DetailsAdults, all genders
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 18-90 years
  • PaO2/FiO2 (PFI) below 200 mmHg (26.7 kPa)
  • Suspected or verified SARS-CoV-2 infection
  • 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
  • Documented informed consent according to ICH-GCP and national regulations

You may not qualify if:

  • ARDS/pneumonia caused by other viral infections (positive for other virus)
  • ARDS/pneumonia caused by other non-viral infections or trauma
  • Known pregnancy or positive pregnancy test in women of childbearing age
  • Patients with previous lung fibrosis more than 10%
  • CT- or Spirometry-verified severe COPD with Emphysema
  • Contraindication for HBO according to local guidelines
  • Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Krankenhaus St. Joesf

Regensburg, 93053, Germany

Location

Blekingesjukhuset

Karlskrona, Blekinge County, Sweden

Location

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (7)

  • Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

    PMID: 32171076BACKGROUND

  • 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.

    PMID: 31537473BACKGROUND

  • Thibodeaux K, Speyrer M, Raza A, Yaakov R, Serena TE. Hyperbaric oxygen therapy in preventing mechanical ventilation in COVID-19 patients: a retrospective case series. J Wound Care. 2020 May 1;29(Sup5a):S4-S8. doi: 10.12968/jowc.2020.29.Sup5a.S4.

    PMID: 32412891BACKGROUND

  • 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.

    PMID: 32931666BACKGROUND

  • 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.

    PMID: 33254531BACKGROUND

  • Kjellberg A, Douglas J, Hassler A, Al-Ezerjawi S, Bostrom E, Abdel-Halim L, Liwenborg L, Hetting E, Jonasdottir Njastad AD, Kowalski J, Catrina SB, Rodriguez-Wallberg KA, Lindholm P. COVID-19-Induced Acute Respiratory Distress Syndrome Treated with Hyperbaric Oxygen: Interim Safety Report from a Randomized Clinical Trial (COVID-19-HBO). J Clin Med. 2023 Jul 24;12(14):4850. doi: 10.3390/jcm12144850.

    PMID: 37510965DERIVED

  • 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.

    PMID: 34226219DERIVED

Related Links

MeSH Terms

Conditions

Severe Acute Respiratory SyndromeCytokine Release SyndromeRespiratory Distress SyndromeCOVID-19

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract DiseasesSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and SymptomsShockLung DiseasesRespiration DisordersPneumonia, ViralPneumonia

Intervention Hierarchy (Ancestors)

Oxygen Inhalation TherapyRespiratory TherapyTherapeutics

Study Officials

  • Anders Kjellberg, MD

    Karolinska Institutet

    PRINCIPAL INVESTIGATOR

  • Peter Lindholm, MD, PhD

    Karolinska Institutet

    STUDY CHAIR

  • Kenny Rodriguez-Wallberg, MD, PhD

    Karolinska Institutet

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized controlled, open label, multi-centre clinical trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
ICU Consultant/PhD student

Study Record Dates

First Submitted

March 25, 2020

First Posted

March 31, 2020

Study Start

June 3, 2020

Primary Completion

June 30, 2022

Study Completion

December 1, 2022

Last Updated

January 9, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will share

The full study protocol, statistical plan and consent form will be publicly available when results are published. Data will be available on patient level; data will be pseudonymized. The full dataset and statistical code will be available upon request.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
Starting after publication and for 36 months
Access Criteria
A full description of the intended use of the data must be sent to the corresponding author for review and approval. Participant consent for data sharing is conditioned and new ethics approval may be required.

Locations

SE(2)DE(1)