Safety and Efficacy of Hyperbaric Oxygen Therapy for Long COVID Syndrome

NCT04842448 | Completed Phase 2 DMC

• 6 other identifiers: HOT-LoCO2021-000764-30K 2021-15924-621/20212022-00834RS 2022-0674
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Long COVID Syndrome (Long COVID), Post Acute COVID-19 Syndrome (PACS) or Post COVID-19 Syndrome (PCS) is defined as 'signs and symptoms that develop during or following an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis'. 1 in 10 infected individuals may suffer persistent symptoms, and we are facing an emerging problem that will severely affect individuals, health care systems and society for years to come. We explore hyperbaric oxygen administered in a randomized placebo-controlled clinical trial as a potential treatment for patients suffering from Long COVID. The overall hypothesis to be evaluated is that hyperbaric oxygen (HBO2) alleviates symptoms associated with Long COVID.

Conditions

COVID-19; Post COVID-19 Condition; Post COVID-19 Condition, Unspecified; Post COVID Condition; Post-COVID Syndrome; Post-Acute COVID-19 Syndrome

Keywords

Long COVID; Post COVID Syndrome; COVID-19; Hyperbaric Oxygen; HBOT; Health Related Quality of Life; Endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• RAND 36 change

  Mean change from baseline to 13 weeks in RAND 36 domains role limitations due to physical health (RP) and physical functioning (PF). RAND 36 is a self-reporting questionnaire that contains 36 items that measure eight concepts of health in general terms, at present and past four weeks. Numeric values from the survey are coded so that all items are scored from 0 (lowest score) to 100 (highest possible score). Scores then represent the percentage of total possible score achieved. Items in the same scale are averaged together to create the eight scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.

  Baseline and 13 weeks

Secondary Outcomes (5)

• Endothelial dysfunction

  Baseline and 13 weeks

• 6-min walk test

  Baseline and 13 weeks

• 30/60 min chair stand

  Baseline and 13 weeks

• EQ-5D

  Baseline and 13 weeks

• RAND 36 normalization

  Baseline and 13 weeks

Other Outcomes (13)

• Adverse Events (AE)

  Baseline and 13 weeks

• Compliance

  Baseline and 13 weeks

• RAND 36 longitudinal

  Baseline, 13 weeks, 26 weeks and 52 weeks

Study Arms (2)

Hyperbaric oxygen treatment

EXPERIMENTAL

HBO2 240 kPa, 90 min, maximum 10 treatments

Drug: Hyperbaric oxygen

Sham treatment

PLACEBO COMPARATOR

Air 134-120 kPa, 90 min, maximum 10 treatments

Procedure: Sham treatment

Interventions

Hyperbaric oxygen DRUG

Hyperbaric oxygen 240 kPa for 90 minutes (with 10 min compression time, 2 air bakes and 10 minutes decompression time).

Also known as: HBO, HBO2, HBOT

Hyperbaric oxygen treatment

Sham treatment PROCEDURE

Sham treatment 134-120 kPa Air (with 5 min compression time, and 5 min decompression to 120 kPa, two air brakes will be reported to the subjects)

Also known as: Placebo

Sham treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-60 years
• Healthy or mild systemic disease (ASA 1-2) prior to COVID-19
• Symptoms consistent with Long COVID for at least 12 weeks
• Diagnosed with Long COVID, PACS, PCS (ICD-10 U09.9)
• Working or studying prior to COVID-19
• Documented informed consent according to GCP and national regulations

You may not qualify if:

• Known pregnancy or positive pregnancy test in women of childbearing age
• ASA 3 or more from other cause than Long COVID
• Score above 70 in RAND-36 Role Limitation Physical Health (RP) or Physical Functioning (PF)
• Diabetes
• Diagnosed with hypertension prior to COVID-19
• Contraindication for hyperbaric oxygen treatment according to local guidelines
• Participation or recent participation in a clinical trial with an investigational product
• Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Karolinska Institutet: collaborator
• Karolinska Trial Alliance: collaborator
• EDC Scandinavia AB: collaborator
• Swedish Heart Lung Foundation: collaborator
• Region Stockholm: collaborator
• The Swedish Research Council: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (6)

• Venkatesan P. NICE guideline on long COVID. Lancet Respir Med. 2021 Feb;9(2):129. doi: 10.1016/S2213-2600(21)00031-X. Epub 2021 Jan 13. No abstract available.

  PMID: 33453162 BACKGROUND

• Dani M, Dirksen A, Taraborrelli P, Torocastro M, Panagopoulos D, Sutton R, Lim PB. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021 Jan;21(1):e63-e67. doi: 10.7861/clinmed.2020-0896. Epub 2020 Nov 26.

  PMID: 33243837 BACKGROUND

• 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: 33254531 BACKGROUND

• Kjellberg A, Abdel-Halim L, Hassler A, El Gharbi S, Al-Ezerjawi S, Bostrom E, Sundberg CJ, Pernow J, Medson K, Kowalski JH, Rodriguez-Wallberg KA, Zheng X, Catrina S, Runold M, Stahlberg M, Bruchfeld J, Nygren-Bonnier M, Lindholm P. Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial. BMJ Open. 2022 Nov 2;12(11):e061870. doi: 10.1136/bmjopen-2022-061870.

  PMID: 36323462 BACKGROUND

• Kjellberg A, Hassler A, Bostrom E, El Gharbi S, Al-Ezerjawi S, Schening A, Fischer K, Kowalski JH, Rodriguez-Wallberg KA, Bruchfeld J, Stahlberg M, Nygren-Bonnier M, Runold M, Lindholm P. Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial. BMJ Open. 2025 Apr 14;15(4):e094386. doi: 10.1136/bmjopen-2024-094386.

  PMID: 40228859 DERIVED

• Kjellberg A, Hassler A, Bostrom E, El Gharbi S, Al-Ezerjawi S, Kowalski J, Rodriguez-Wallberg KA, Bruchfeld J, Stahlberg M, Nygren-Bonnier M, Runold M, Lindholm P. Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial. BMC Infect Dis. 2023 Jan 20;23(1):33. doi: 10.1186/s12879-023-08002-8.

  PMID: 36670365 DERIVED

Related Links

• Research group Hyperbaric Medicine at Karolinska Institutet

MeSH Terms

Conditions

COVID-19; Post-Acute COVID-19 Syndrome

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Anders Kjellberg, MD, PhD

  Karolinska University Hospital (and Karolinska Insitutet)

  PRINCIPAL INVESTIGATOR

• Judith Bruchfeld, MD, PhD

  Karolinska University Hospital (and Karolinska Insitutet)

  STUDY CHAIR

• Malin Nygren-Bonnier, PhD

  Karolinska University Hospital (and Karolinska Insitutet)

  STUDY CHAIR

• Michael Runold, MD, PhD

  Karolinska University Hospital (and Karolinska Insitutet)

  STUDY CHAIR

• Marcus Ståhlberg, MD, PhD

  Karolinska University Hospital (and Karolinska Insitutet)

  STUDY CHAIR

• Peter Lindholm, MD, PhD

  Karolinska Insitutet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be randomized to either active treatment or sham treatment. Assessors will be blinded to treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ICU Consultant, head of hyperbaric medicine

Model Details: Randomized, placebo-controlled, double-blind, phase II

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 13, 2021
• Study Start: September 15, 2021
• Primary Completion: September 27, 2023
• Study Completion: June 17, 2024
• Last Updated: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after study completion 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 (1)