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

Background: 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).