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

COVID-19 Clinical Trial

— COVID-19-HBO  

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

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
• 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
• 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)

Related Conditions & MeSH terms

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

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

External Links

•   COVID-19 EUBS-ECHM position statement on HBOT
•   Hyperbaric medicine research group, Karolinska Institutet
•   KI News-description of trial in layman language
•   UHMS position statement and information on HBO for COVID-19