Trial Report Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid HOT-LoCO…, 2025, Kjellberg et al.

SNT Gatchaman

SNT Gatchaman

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Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid HOT-LoCO: a randomised, placebo-controlled, double-blind, phase II trial
Anders Kjellberg; Adrian Hassler; Emil Boström; Sara El Gharbi; Sarah Al-Ezerjawi; Anna Schening; Katarina Fischer; Jan H Kowalski; Kenny A Rodriguez-Wallberg; Judith Bruchfeld; Marcus Ståhlberg; Malin Nygren-Bonnier; Michael Runold; Peter Lindholm

OBJECTIVES
To evaluate if 10 sessions of hyperbaric oxygen treatments (HBOTs) improve short-and long-term health related quality of life, symptoms and physical performance in long covid patients compared with placebo.

DESIGN
Parallel, randomised, placebo-controlled, double-blind trial.

SETTING
Single-centre, university hospital, Sweden.

PARTICIPANTS
Previously healthy subjects aged 18–60 years, diagnosed with long covid were included. We excluded pregnant women, patients with RAND-36 (role limitations due to physical health (RP) and physical functioning (PF)) above 70, diabetes, hypertension and contraindications for HBOT.

INTERVENTIONS
Subjects were randomly assigned to 10 sessions of HBOT or sham (placebo) treatments over 6 weeks. HBOT involved 100% oxygen, 2.4 bar, 90 min, placebo medical air, 1.34–1.2 bar. Randomisation (1:1) was done electronically, in blocks stratified by sex and disease severity. Subjects and investigators were blinded to allocation.

PRIMARY AND SECONDARY OUTCOME MEASURES
Primary endpoints were changes from baseline in RAND-36 PF and RP at 13 weeks. Efficacy was analysed on an intention-to-treat basis. Harms were evaluated according to the actual treatment given.

RESULTS
Between 15 September 2021 and 20 June 2023, 80 subjects (65 women, 15 men) were enrolled and randomised (40 in each group). The trial is completed. The primary endpoint analysis included 79 subjects (40 in HBOT and 39 in control). At 13 weeks, both groups showed improvement, with no significant difference between HBOT and placebo in PF (least square mean difference between groups (LSD), 0.63 (95% CI −7.04 to 8.29), p=0.87) and RP (LSD, 2.35 (95% CI −5.95 to 10.66), p=0.57). Harms: 43 adverse events (AEs), most commonly cough and chest pain/discomfort, occurred in 19 subjects (49%) of the HBOT group and 38 AEs in 18 subjects (44%) of the placebo group, one serious AE in HBOT and one death in the placebo group.

CONCLUSIONS
10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved, with a notable sex difference. HBOT has a favourable harm profile.

TRIAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT04842448), EudraCT (2021-000764-30). The trial was funded by Vetenskapsradet (2022-00834), Region Stockholm (2020-0731, 2022-0674), Hjart-Lungfonden and OuraHealth Oy.


Link | PDF (BMJ Open) [Open Access]
 
Since they found no difference in outcome, does it matter if some patients could tell which group they were in?

It's good this has been done, as I recall early in the pandemic people with Long Covid were wasting money on sessions of HBOT.
 
Trish said:
Since they found no difference in outcome, does it matter if some patients could tell which group they were in?
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You're right, it doesn't - I misread the abstract and thought it said that the HBOT showed 'no more than' short-term benefits, rather than 'showed no more benefits'. o_O
 
The placebo protocol is well established, and even experienced divers cannot differentiate between ‘sham treatment’ and HBOT.24 The success of the masking procedure was validated by asking the subjects to guess the allocated treatment after the first treatment.
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Eligible subjects at visit 1 were randomised and received a maximum of 10 HBOT or placebo (sham) treatments over 6 weeks from randomisation, the recommended scheme was every 2–3 days. Medical oxygen 100% was administered at 2.4 ATA for 90 min with two 5 min air breaks (rebreather mask). Sham treatment with medical air was administered by increasing pressure briefly to 1.34 ATA and then reduced and maintained at 1.2 ATA for 90 min with two 5 min air breaks (rebreather mask)
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The primary endpoints were
  • the physical domains, PF and RP, in the RAND 36-Item Health Survey 1.0 at 13 weeks
The main secondary endpoints were
  • the physical tests 6MWT and 30-seconds CST
  • European Quality of Life-5 Dimensions-5 Level version (EQ-5D-5L)
  • objective evaluation of endothelial function with reactive hyperaemia index at 13 weeks
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Bullet points added.
They also used an Oura ring for HRV and sleep tracking.
 
F2.large.jpg

It might be personal preference, but I really wish they included more graphs.
 
Trish said:
Since they found no difference in outcome, does it matter if some patients could tell which group they were in?

It's good this has been done, as I recall early in the pandemic people with Long Covid were wasting money on sessions of HBOT.
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I’ve heard of stories where people pushed themselves to do it and ended up having permanent worsenings of the illness… (which they attributed to overexerting because they were convinced HBOT would work)
 
Not read the paper, but wanted to commend this publication of null results, we need to be able to rule out as much as possible these distractions syphoning money and time from patients desperately seeking anything to help.

We need health care to be more upfront about the current lack of evidence for any evidenced treatment for ME/CFS and Long Covid meeting the diagnostic criteria for ME/CFS. This lack of honesty not only wastes resources it also undermines patients making meaningful adaptations.
 
rapidboson said:
Isn't 40 sessions commonly done for HBOT & LC or ME? 8 Weeks of 5 sessions/week. The 10 sessions discussed here seem quite little in comparison.
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From the paper, linebreaks added:

HBOT with 40 sessions at 2.0 atmospheres absolute (ATA), 90 min with 5 min air breaks every 20 min has been shown to improve neurocognitive function and symptoms.

Clinical improvement was associated with changes on MRI and improvement of myocardial function in long covid in a randomised, placebo-controlled trial.10 11

A longitudinal follow-up of selected subjects from the phase II trial suggests a sustained effect for 3 months but high-grade evidence for long-term efficacy compared with a control group is missing.12

HBOT has previously been suggested to be effective in chronic fatigue syndrome with only 15 sessions.13 Two case series with 32 patients suggest efficacy from 10 sessions at 2.2–2.4 ATA, 75–105 min with two 5 min air breaks, but no Randomised Controlled Trials (RCTs) are published on this dose.

A shorter treatment with 10–15 sessions has become increasingly popular off-label for long covid.14

The rationale for using fewer and less frequent sessions for long covid is based on the hyperoxic–hypoxic paradox with downstream regulation of hypoxia and inflammatory pathways,15previous clinical experience from severe COVID-19 and experimental research.16 17
 
rapidboson said:
That's not the point I'm making. I never said their trial design is optimal, I merely used them as examples for 40 sessions seemingly being the latest protocol. Hence, 10 sessions seemed little.
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I never said you said so. I just made a comment on the design of the trials.

Please see my other comment where I’ve read the paper to answer your question.
 
Utsikt said:
I never said you said so.
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And I never said that you said that I said... I guess you see this rhetoric leads us nowhere.

From your other comment I read their reasoning, but personally not convinced their reasoning makes much sense. Thanks for the excerpt!
 
rapidboson said:
From your other comment I read their reasoning, but personally not convinced their reasoning makes much sense. Thanks for the excerpt!
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What doesn’t make sense to you?

It seems to me like they’ve observed clinically and empirically that a lower dose might be effective, and they believe there is a rationale for it, so they wanted to test if it was.

Is it the rationale that you don’t agree with?
 
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The paper said:
10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved
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This is exactly what the psychobehaviorists exploit when they go for within group differences that ultimately barely differ between groups. Even more so when they do like PACE and cross over the arms, then do a post-hoc analysis anyway. Although there seems to be a slight benefit from HBOT, it doesn't seem significant. If this were a BPS study, it would have been hailed as promising.
Peter Trewhitt said:
Not read the paper, but wanted to commend this publication of null results, we need to be able to rule out as much as possible these distractions syphoning money and time from patients desperately seeking anything to help.

We need health care to be more upfront about the current lack of evidence for any evidenced treatment for ME/CFS and Long Covid meeting the diagnostic criteria for ME/CFS. This lack of honesty not only wastes resources it also undermines patients making meaningful adaptations.
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It's probably a lot easier for journals to be interested in publishing null results about treatments they don't expect, or want, to work. Similar to Garner's early review of plasmapheresis, published by Cochrane because they don't want it to be an effective treatment, whereas for psychobehavioral stuff they badly want it to be true, and don't have the same interest in null results.
Trish said:
Since they found no difference in outcome, does it matter if some patients could tell which group they were in?

It's good this has been done, as I recall early in the pandemic people with Long Covid were wasting money on sessions of HBOT.
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The difference with the patient community is that we accept that treatments don't work, and leave them behind. At the time it started being suggested, there were lots of posts on the LC sub-reddit. I maybe remember 1-2 in the last 2 years. Because we have all the stakes, we are eager to abandon things that don't work, have no investment in them.
 
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