Anders Kjellberg

Background: Necrotizing soft tissue infections (NSTI) is a debilitating and potentially life-threatening condition that needs urgent multidisciplinary management including broad spectrum antibiotics, surgery, and intensive care support. Hyperbaric oxygen therapy (HBOT) is used as an adjuvant treatment since 60 years but evidence is limited to small cohorts and retrospective data. Current evidence suggests a strong correlation between HBOT and decreased mortality [RR = 0.522, 95% CI (0.403, 0.677), p < 0.05], but there is still clinical equipoise regarding the causal effect. Aim: We aim to plan and conduct an international multicenter randomized controlled trial (RCT) including 1300 patients in collaboration with 15+ centers. Hypothesis: We hypothesize that the use of adjuvant HBOT in NSTI will increase the effect of antibiotics, reduce multi-organ failure and as a result reduce mortality. Objective: The primary objective is to evaluate if HBOT can reduce 30-day mortality in NSTI. Secondary objectives include evaluation if HBOT can reduce multi-organ failure, ICUmortality, 90-day mortality and amputations. Other objectives include evaluation of safety, exploration of mechanisms, long term outcome, quality of life and health economic aspects. Trial design: International multicenter, parallel-arms, single-blinded, RCT conducted in compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH)-Good Clinical Practice (ICH-GCP).

Post covid condition (PCC) affects approximately 10% of people infected with SARS-CoV-2. With half a billion confirmed COVID-19 cases globally, the magnitude of the expected Post COVID healthcare problem is enormous. No treatment options to date have shown efficacy. Aims: To investigate biomarkers, redox-balance and epigenetic profile of patients with PCC To determine the efficacy of HBOT on endothelial dysfunction, objective physical performance, autonomic dysfunction, restorative sleep. To investigate if the effect of HBOT in PCC in a clinical trial correlates with age, gender and epigenetic signatures. Preliminary results from our clinical trial on 31 acute covid-19 indicates effect from HBO but treatment may need individual tailoring. To date we have treated 20 PCC patients, aiming for a total of 80 participants.We hypothesize that part of PCC is a chronic inflammation involving the endothelium started by COVID-19 and treatable by the anti-inflammatory effects of hyperbaric oxygen (HBO2). HBO2 delivered by inhalation of 100% oxygen in a hyperbaric chamber in daily treatments over several weeks, has several anti-inflammatory effects. It is used for chronic inflammatory conditions such as osteomyelitis, radiation cystitis and acute flares of ulcerative colitis. The purpose of this proposal is to investigate biomarkers, epigenetic signatures and response to HBO2 in a clinical trial that may explain mechanisms of the post COVID condition and enable future precision medicine.