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).