Efficacy and Safety of Dalbavancin in the Treatment of Infective Endocarditis Caused by Gram-Positive Cocci (EndoDalba)

• Applicant: Privatdozent Dr. Stefan Hagel
• Subject Area: Clinical Infectiology and Tropical Medicine ; Cardiac and Vascular Surgery ; Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530334941

Endocarditis, an infection of the heart valves, affects up to 10 out of 100,000 individuals per year, with an annual incidence increasing by 4.1%. Mortality remains unchanged at 30% after one year, with gram-positive bacteria responsible for over 90% of cases. Antibiotic treatment lasts 4-6 weeks, and approximately half of the patients require surgery. Previously, there was a consensus that the entire antibiotic therapy must be administered intravenously, leading to complications such as vascular catheter infections and delaying discharge, hindering early rehabilitation initiation. In recent years, a switch to oral therapy (tablet administration) has been shown feasible in selected cases. However, unpredictable oral bioavailability, leading to underdosing and therapy failure, poses a challenge. Oral therapy heavily depends on treatment adherence, with only 50% compliance, especially with four-times-daily dosing. An alternative to prolonged intravenous administration may be Dalbavancin therapy. Dalbavancin, a lipoglycopeptide antibiotic with a half-life of 14.4 days, allows less frequent dosing (every 14 days), facilitating earlier discharge and more effective antibiotic treatment, regardless of compliance. Additionally, it exhibits up to 32 times higher efficacy against gram-positive bacteria, strong biofilm activity, minimal impact on the gut microbiome, and a favorable safety profile compared to other antibiotics. Based on these properties, we aim to examine whether Dalbavancin therapy is superior to standard therapy for individuals with endocarditis caused by gram-positive bacteria. Intervention group participants will receive Dalbavancin according to a dosing schedule based on the remaining duration of antibiotic therapy. Control group participants will receive antibiotic therapy according to current guidelines, including the option of sequential intravenous-oral therapy once specific clinical stability criteria are met. The primary endpoint is the comparison of the Desirability Of Outcome Ranking (DOOR) at Day 90. DOOR is a novel approach to assessing the overall benefits and risks of an intervention, providing more pragmatic information for medical decision-making. Five DOOR endpoints will be ranked, considering both efficacy and toxicity, including survival status, treatment failure, and adverse events. A total of 166 participants are planned to be recruited.

• DFG Programme: Clinical Trials
• Co-Investigators: Professor Dr. Torsten Doenst; Professor Dr. Christian Schulze