Dalbavancin Therapy for Infective Endocarditis (EndoDalba)

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

This study compares two treatment strategies for antibiotic therapy in endocarditis. The aim of the study is to determine which treatment is more effective overall and better tolerated by patients.

The first strategy is standard therapy: treatment with proven antibiotics, which are usually administered initially as an intravenous infusion in the hospital and can be switched to oral therapy with tablets later on for suitable patients.

The second strategy is the study treatment with dalbavancin: This is a long-acting antibiotic. It is administered as a single infusion; for longer treatment durations, a second infusion may be necessary 14 days later.

Study Overview

• Status: Not yet recruiting
• Conditions: Endocarditis, Bacterial; Endocarditis Infective
• Intervention / Treatment: Drug: Dalbavancin administration; Drug: Standard of Care (Investigator Choice)

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Stefan Hagel, PD Dr.; Phone Number: +4936419324590; Email: stefan.hagel@med.uni-jena.de

Study Locations

• Germany
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • Universitätsklinikum Freiburg
      • Contact: Siegbert Richard Sieg, Prof. Dr.; Phone Number: +4976127018190; Email: siegbert.rieg@uniklinik-freiburg.de
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Universitätsklinikum Regensburg
      • Contact: Frank Hanses, Prof. Dr.; Phone Number: +4994414251; Email: frank.hanses@klinik.uni-regensburg.de
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20246
      • Universitatsklinikum Hamburg-Eppendorf
      • Contact: Stefan Schmiedel, Dr.; Phone Number: +4940741028532; Email: s.schmiedel@uke.de
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitätsklinikum Köln
      • Contact: Norma Jung, Prof. Dr.; Phone Number: +4922147886711; Email: norma.jung@uk-koeln.de
  • Saxony
    • Leipzig, Saxony, Germany, 04129
      • Klinikum St. Gerog gGmbh
      • Contact: Christoph Lübbert, Prof. Dr.; Phone Number: +493419092601; Email: Christoph.Luebbert@medizin.uni-leipzig.de
  • State of Berlin
    • Berlin, State of Berlin, Germany, 12157
      • Vivantes Auguste-Viktoria-Klinikum
      • Contact: Daniela Tominski, Dr.; Phone Number: +49130202321; Email: daniela.tominski@vivantes.de
    • Berlin, State of Berlin, Germany, 13353
      • Deutsches Herzzentrum der Charité (DHZC)
      • Contact: Miriam Stegemann, Dr.; Phone Number: +4930450665037; Email: miriam.stegemann@charite.de
  • Thuringia
    • Erfurt, Thuringia, Germany, 99089
      • Helios Klinikum Erfurt GmbH
      • Contact: Alexander Lauten, Prof. Dr.; Phone Number: +493617812481; Email: Alexander.Lauten@helios-gesundheit.de
    • Jena, Thuringia, Germany, 07747
      • University Hospital Jena
      • Contact: Stefan Hagel, PD Dr.; Phone Number: +4936419324590; Email: stefan.hagel@med.uni-jena.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years
2. written informed consent
3. Confirmed left-sided infective endocarditis (mitral and/or aortic valve) involving native (NV) or prosthetic (PV) valves caused by Gram-positive cocci (staphylococci, streptococci, or enterococci) that are susceptible to dalbavancin.

Exclusion Criteria:

1. Hemodynamic instability requiring vasopressor therapy within the last 72 hours prior to randomization
2. Body temperature ≥38.0°C within the 72 hours prior to randomization
3. Evidence of pathogen growth in a blood culture within the 72 hours prior to randomization
4. Presence of a cardiac abscess at the time of randomization
5. Presence of a remaining infected cardiovascular implantable electronic device (CIED), an infected intravascular graft, or an infected TAVI prosthesis ("TAVI endocarditis") at the time of randomization
6. Duration of effective intravenous antibiotic therapy for endocarditis of < 7 days prior to randomization
7. Remaining duration of required antibiotic therapy for the treatment of endocarditis is less than 10 days (i.e., remaining treatment duration must be at least 10 days)
8. Hypersensitivity to dalbavancin, vancomycin, teicoplanin, or other components of the investigational drug
9. Participation in another clinical interventional trial under the German Medicines Act (AMG), Medical Devices Regulation (MDR), or Medical Devices Act (MPDG) without prior consultation and approval by the respective sponsors prior to randomization
10. Continuous renal replacement therapy (e.g., CVVHD, CVVHDF)
11. Child B or C liver cirrhosis
12. Palliative care
13. Secondary infections requiring a longer course of antibiotic therapy than that intended for the treatment of endocarditis
14. Oral antibiotic therapy already initiated to treat the current episode of endocarditis
15. Scheduled cardiac surgery after randomization, within the period designated for antibiotic treatment of endocarditis
16. Intraspinal or brain abscess (> 0.5 cm)
17. Pregnant and breastfeeding women

18. Women of childbearing potential, unless the following criteria are met:

    1. Postmenopausal (12 months of natural amenorrhea or 6 months of amenorrhea with serum FSH > 40 mIU/mL)
    2. Postoperative (6 weeks after bilateral oophorectomy with or without hysterectomy)
    3. Regular and correct use of a contraceptive method with a failure rate < 1% per year (considered reliable contraceptive methods include oral hormonal contraception, dermal hormonal contraception, contraceptive patches, long-acting injectable contraceptives, progesterone-releasing implants (Implanon®), intramuscular progesterone, tubal ligation (female sterilization), hormone-releasing intrauterine device ("hormonal IUD"), dual barrier methods)
    4. sexual abstinence
    5. Vasectomy of the partner

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: intervention group; Dalbavancin 500 mg; intravenous, 30-minute infusion duration per administration	Drug: Dalbavancin administration; Dosage: Total dose depending on the required duration of therapy for endocarditis Route of administration: intravenous, 30-minute infusion duration per administration Frequency: Day 0 and, if necessary, an additional administration on Day 14 ± 2 days, depending on the required duration of therapy for endocarditis Duration of treatment: depending on the required duration of therapy for endocarditis (2-5 weeks)
Other: control group; Therapy in accordance with the recommendations of the current European Society of Cardiology (ESC) guidelines for the treatment of endocarditis, including oral sequential therapy	Drug: Standard of Care (Investigator Choice); Therapy in accordance with the recommendations of the current European Society of Cardiology (ESC) guidelines for the treatment of endocarditis, including oral sequential therapy Test drug: depending on pathogen, resistance, and comorbidities Dosage: depending on pathogen, resistance, and comorbidities Route of administration: intravenous, including oral sequential therapy Duration of treatment: depending on the required treatment duration for endocarditis (2-5 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the Desirability of Outcome Ranking (DOOR) on Day 90 between patients treated with dalbavancin and those treated with standard therapy	Five possible DOOR ratings are distinguished: Alive, no events; Alive, one event; Alive, two events; Alive, three events; Death within 90 days Door events include: Cardiac surgery; Infectious complication; Embolic event	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay (days)		Day 90
National Institutes of Health Stroke Scale (NIHSS)	Scores range from 0 to 42, where 0 indicates normal function and higher numbers reflect greater impairment	Day 90 and 1 year
PROMIS-29 domain-specific T-scores and pain intensity	The PROMIS-29 assesses physical, mental, and social health using 7 domains (4 items each) and pain intensity (1 item). A higher Domain-Specific T-Score (scale range 20-80) means a better outcome for functional domains (Physical Function, Social Roles) but a worse outcome for symptom domains (Anxiety, Depression, Fatigue, Sleep Disturbance). Pain intensity is recorded on an 11-point numeric scale (0-10, where 0 is "no pain" and 10 is "worst imaginable").	Day 90 and 1 year
Overall mortality		Day 90 and 1 year
Cardiac surgery		Day 90 and 1 year
Infectious complications		Day 90 and 1 year
Embolic event		Day 90 and 1 year
Clinical Frailty Scale	The Clinical Frailty Scale (CFS) ranges from a minimum of 1 (representing "very fit") to a maximum of 9 (representing "terminally ill"), meaning a higher score indicates a WORSE outcome (reflecting a higher level of frailty).	Day 90 and 1 year
Occurrence of treatment-related adverse events		Baseline to End of Therapy +14 days
Dalbavancin Plasma Concentration	Through level, mg/l	Day 1, Day 2, Day 14, and if applicable, Day 2, Day 28, Day 35
Microbiome analysis	Shannon Diversity Index, 1-5 range, Generally, a higher score indicates a BETTER outcome	Baseline, Day 90 and 1 year
Cost of antibiotic therapy		Day 90
Number of days of work disability		Day 90
modified Rankin Scale (mRS)	7-point clinical scale used to measure the degree of disability or dependence in the daily activities. Scores range from 0 (no symptoms) to 6 (dead)	Day 90 and 1 year
EQ-5D-5L index	EuroQuality of Life Five Dimensions (EQ-5D-5L), the descriptive system comprises five dimensions (MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION), with five response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems.	Day 90 and 1 year
Reintegration to Normal Living Index (RNLI)	The Reintegration to Normal Living Index (RNLI) Total Adjusted Score ranges from a minimum of 0 to a maximum of 100, meaning a higher score indicates a BETTER outcome (reflecting full or complete reintegration into normal social activities	Day 90 and 1 year

Collaborators and Investigators

• Sponsor: Stefan Hagel

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: June 29, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Dalbavancin; Infective Endocarditis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Endocarditis; Endocarditis, Bacterial; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: ZKSJ0165; 2026-526149-91-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No