Kjellberg A, Abdel-Halim L, Hassler A, El Gharbi S, Al-Ezerjawi S, Boström E, Sundberg CJ, Pernow J, Medson K, Kowalski JH, Rodriguez-Wallberg KA, Zheng X, Catrina S, Runold M, Ståhlberg M, Bruchfeld J, Nygren-Bonnier M, Lindholm P, et al.
BMJ open. Date of publication 2022 Nov 2;volume 12(11):e061870.
1. BMJ Open. 2022 Nov 2;12(11):e061870. doi: 10.1136/bmjopen-2022-061870.
Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol
for a randomised, placebo-controlled, double-blind, phase II clinical trial.
Kjellberg A(1)(2), Abdel-Halim L(3), Hassler A(3)(4), El Gharbi S(3)(4),
Al-Ezerjawi S(3)(4), Boström E(3)(4), Sundberg CJ(3)(5), Pernow J(6)(7), Medson
K(3)(8), Kowalski JH(9), Rodriguez-Wallberg KA(10)(11), Zheng X(12), Catrina
S(12)(13), Runold M(14)(15), Ståhlberg M(7)(16), Bruchfeld J(17)(18),
Nygren-Bonnier M(19)(20), Lindholm P(3)(21).
Author information:
(1)Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm,
Sweden anders.kjellberg@ki.se.
(2)Perioperative Medicine and Intensive Care, Medical Unit Intensive Care and
Thoracic Surgery, Karolinska University Hospital, Stockholm, Sweden.
(3)Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm,
Sweden.
(4)Medical Unit Emergency Medicine, Karolinska University Hospital, Stockholm,
Sweden.
(5)Department of Learning, Informatics, Management and Ethics, Karolinska
Institutet, Stockholm, Sweden.
(6)Division of Cardiology, Heart and Vascular Theme, Karolinska University
Hospital, Stockholm, Sweden.
(7)Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
(8)Department of Imaging and Physiology, Karolinska University Hospital,
Stockholm, Sweden.
(9)EDC Scandinavia, Stockholm, Sweden.
(10)Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
(11)Department of Reproductive Medicine, Division of Gynecology and
Reproduction, Karolinska University Hospital, Stockholm, Sweden.
(12)Department of Molecular Medicine and Surgery, Karolinska Institutet,
Stockholm, Sweden.
(13)Center for Diabetes, Academic Specialist Center, Stockholm, Sweden.
(14)Department of Medicine Solna, Respiratory Medicine Unit, Karolinska
Institutet, Stockholm, Sweden.
(15)Department of Respiratory Medicine and Allergy, Karolinska University
Hospital, Stockholm, Sweden.
(16)ME Cardiology, Heart, Vascular and Neuro Theme, Karolinska University
Hospital, Stockholm, Sweden.
(17)Department of Infectious Diseases, Karolinska University Hospital,
Stockholm, Sweden.
(18)Department of Medicine Solna, Division of Infection Diseases, Karolinska
Institutet, Stockholm, Sweden.
(19)Department of Neurobiology, Care Sciences and Society, Division of
Physiotherapy, Karolinska Institutet, Stockholm, Sweden.
(20)Women's Health and Allied Health Professionals Theme, Medical Unit
Occupational Therapy and Physiotherapy, Karolinska University Hospital,
Stockholm, Sweden.
(21)Department of Emergency Medicine, Division of Hyperbaric medicine, UCSD, La
Jolla, California, USA.
INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial
SARS-CoV-2-infection, is a substantial problem for individuals and society in
the surge of the pandemic. Common symptoms are fatigue, postexertional malaise
and cognitive dysfunction. There is currently no effective treatment and the
underlying mechanisms are unknown, although several hypotheses exist, with
chronic inflammation as a common denominator. In prospective studies, hyperbaric
oxygen therapy (HBOT) has been suggested to be effective for the treatment of
similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case
series has suggested positive effects of HBOT in long COVID-19. This randomised,
placebo-controlled clinical trial will explore HBOT as a potential treatment for
long COVID-19. The primary objective is to evaluate if HBOT improves
health-related quality of life (HRQoL) for patients with long COVID-19 compared
with placebo/sham. The main secondary objective is to evaluate whether HBOT
improves endothelial function, objective physical performance and short-term
HRQoL.
METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II
clinical trial in 80 previously healthy subjects debilitated due to long
COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples,
objective tests and activity metre data will be collected at baseline. Subjects
will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham
treatment over 6 weeks. Assessments for safety and efficacy will be performed at
6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND
36-Item Health Survey) and main secondary endpoints defined at 13 weeks after
baseline. Data will be reviewed by an independent data safety monitoring board.
ETHICS AND DISSEMINATION: The trial is approved by the Swedish National
Institutional Review Board (2021-02634) and the Swedish Medical Products Agency
(5.1-2020-36673). Positive, negative and inconclusive results will be published
in peer-reviewed scientific journals with open access.
TRIAL REGISTRATION NUMBER: NCT04842448.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No
commercial re-use. See rights and permissions. Published by BMJ.
DOI: 10.1136/bmjopen-2022-061870
PMCID: PMC9638753
PMID: 36323462 [Indexed for MEDLINE]
Conflict of interest statement: Competing interests: AK and PL disclose funding
from Swedish Heart-Lung Foundation (HLF) and Stockholm Health Council for the
present trial. AK disclose funding from Oura Health Oy with complimentary
hardware and software for the Oura rings. MS discloses funding from Swedish
Research Council and Dysautonomia International during the trial and previously
from HLF. MS also disclose consulting fees from the Swedish Agency for Health
Technology Assessment of Social Services, speaker honoraria from Orion Pharma,
Werfen, and has filed a patent for pharmacological treatment in post-COVID
postural orthostatic tachycardia syndrome. JK declares consulting fee for
statistical work in this trial. LA-H, AH, SEG, SA-E, EB, CJS, JP, KM, KRW, XZ,
SBC, MR, JB and MN-B declare that they have no known competing financial
interests or personal relationships that could have appeared to influence the
work reported in this paper.
