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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04327505
Other study ID # COVID-19-HBO
Secondary ID 2020-001349-37K-
Status Terminated
Phase Phase 2/Phase 3
First received
Last updated
Start date June 3, 2020
Est. completion date December 1, 2022

Study information

Verified date January 2023
Source Karolinska Institutet
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Terminated
Enrollment 34
Est. completion date December 1, 2022
Est. primary completion date June 30, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 90 Years
Eligibility 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Hyperbaric oxygen
1.6- 2.4 ATA, 30-60 min (excluding compression/recompression)

Locations

Country Name City State
Germany Krankenhaus St. Joesf Regensburg
Sweden Blekingesjukhuset Karlskrona Blekinge
Sweden Karolinska University Hospital Stockholm

Sponsors (7)

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

Countries where clinical trial is conducted

Germany,  Sweden, 

References & Publications (5)

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. — View 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. — View 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. Erratum In: Lancet Oncol. 2019 Sep 23;: — View Citation

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. — View Citation

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. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Hospital mortality Hospital mortality of any cause, proportion of subjects, from day 1 to day 30. Through study completion 30 days
Other ICU mortality Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30. From ICU admission to study completion 30 days
Other Time in Invasive Ventilation Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30. From ICU admission to study completion 30 days
Other NEWS Mean daily NEWS from day 1 to day 30. Through study completion 30 days
Other PaO2/FiO2 (PFI) Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30. Through study completion 30 days
Other HBO Compliance Proportion of HBO treatments given vs planned.
Proportion of subjects with HBO treatment administered within 24h after enrolment.
Day 1 to day 7
Other Hospital discharge Time-to-discharge from hospital Through study completion 30 days
Other Oxygen dose 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. Through study completion 30 days
Other HBO dose Median number of HBO treatments and dose of HBO given, from day 1 to day 7 Day 1 to day 7
Other Micro RNA Change in expression of Micro RNA in plasma from day 1 to day 30 Through study completion 30 days
Other Hypoxic response Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) (20 Subjects) from day 1 to day 30 Through study completion 30 days
Other Immunological response Immunological response (20 subjects) from day 1 to day 30 in the following.
Cytokines extended including (IL-1ß, IL-2, IL-6, IL33 and TNFa)
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-1ß, IL-2, IL-6, IL33 and TNFa),
T-reg cells (CD3+/CD4+/CD25+/CD127+)
Monocyte proliferation markers, Ex vivo monocyte function
Through study completion 30 days
Other Multi organ dysfunction Mean change in routine biomarkers for organ dysfunction, from day 1to day 30. Through study completion 30 days
Other Viral load Viral load, review of records from day 1 to day 30. Through study completion 30 days
Other Secondary infections Number of secondary infections, review of records, number of events and patients from day 1 to day 30. Through study completion 30 days
Other Pulmonary embolism Diagnosed PE needing treatment, review of records, number of events and patients from day 1 to day 30. Through study completion 30 days
Other Pulmonary CT Changes on Pulmonary CT, review of records from day 1 to day 30. Through study completion 30 days
Other Chest X-ray Changes on Chest X-ray, review of records from day 1 to day 30. Through study completion 30 days
Other Lung ultrasound Changes in Lung ultrasound, review of records from day 1 to day 30. Through study completion 30 days
Primary 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 30-day mortality Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30. Through study completion 30 days
Secondary Time-to-intubation Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30 Through study completion 30 days
Secondary Time-to-ICU 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. Through study completion 30 days
Secondary Inflammatory response 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
Through study completion 30 days
Secondary Overall survival Overall survival (Kaplan-Meier) Through study completion 30 days
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