Hyperbaric Oxygen Treatment as a Novel Add-on in Selected Patients with Infective Endocarditis – A Safety and Feasibility Trial

Mia Marie Pries-Heje,1 Christian Johann Lerche,2 Emil Fosbøl,1,3 Martin Forchhammer,4,5 Rasmus Bo Hasselbalch,1,5 Franziska Schwartz,2 Anne Sofie L Siebert,2 Peter Østrup Jensen,2,6,7 Henrik Rottensten,4 Kasper Iversen,3,5,8 Henning Bundgaard,1,3 Ole Hyldegaard,3,4 Claus Moser2,6 1Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 2Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 4Department of Anaesthesiology, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen University, Copenhagen, Denmark; 5Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; 6Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; 7Center for Rheumatology and Spine Diseases, Institute for Inflammation Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen; 8Department of Emergency Medicine, Herlev-Gentofte Hospital, Copenhagen University Hospital, Herlev, DenmarkCorrespondence: Mia Marie Pries-Heje, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, 2100, Denmark, Tel +45 35 45 23 40, Email [email protected]: Infective endocarditis (IE) is associated with a high morbidity and mortality. Adjunctive hyperbaric oxygen (HBO2) treatment may enhance bactericidal effects of antibiotics and improve outcomes in patients with IE We conducted an open label, feasibility, and safety trial, including exploratory biomarker analyses, to evaluate HBO2-therapy in patients with IE.Methods: This Phase I/II feasibility and safety trial included patients aged > 18 years, with left-sided IE caused by Gram-positive cocci. The intervention consisted of six consecutive HBO2-sessions at 2.4 atm. Antibiotics were administered 1 hour before each HBO2-session.Results: Of 26 screened patients, 13 patients were included and 10 (77%) completed the HBO2-therapy (age 80 years (IQR 73– 83); 70% male). Median time from diagnosis of IE to first HBO2 session was 6 days (IQR 5– 7). No serious adverse events or suspected unexpected serious adverse reactions were recorded. Pre- and post-HBO2 blood samples revealed significant changes in biomarkers: reduced median CRP levels (22 vs 15 mmol/L, p=0.043) and hemoglobin levels (6.4 vs 5.8 mmol/L, p=0.021); increased mean serum VCAM-1 (1.22x106 vs. 1.29x106 pg/mL, p=0.0003) and E-selectin (5.7x104 vs. 6.41x104 pg/mL, p=0.044); and a decrease in G-CSF levels (73.85 vs 72.93 pg/mL, p=0.021), activated platelets (193.7 vs 169.8 MFI, p=0.015), and platelet-neutrophil complexes (2747 vs 1916 MFI, p=0.003).Conclusion: Adjunctive HBO2 therapy was feasible and safe in selected patients with IE. Significant changes in biochemical markers suggest potential immunomodulatory effects of HBO2-therapy. Randomized controlled trials are required to evaluate the clinical efficacy of HBO2 as an adjunct to standard care in IE.Study Id: EudraCT (2019– 000857-29). Danish Medicines Agency (2019030362). Infographic on hyperbaric oxygen treatment for adults with left-sided IE. Includes population, intervention, sample collection and findings.Keywords: infective endocarditis, hyperbaric oxygen, adjunctive therapy, biofilm infection