Endocarditis, Bacterial, Endocarditis Infective
Conditions
Keywords
Infective Endocarditis, Dalbavancin
Brief summary
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.
Interventions
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)
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)
Sponsors
Stefan Hagel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Desirability of Outcome Ranking (DOOR) on Day 90 between patients treated with dalbavancin and those treated with standard therapy | Day 90 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay (days) | Day 90 | — |
| National Institutes of Health Stroke Scale (NIHSS) | Day 90 and 1 year | Scores range from 0 to 42, where 0 indicates normal function and higher numbers reflect greater impairment |
| PROMIS-29 domain-specific T-scores and pain intensity | Day 90 and 1 year | 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"). |
| 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 | Day 90 and 1 year | 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). |
| Occurrence of treatment-related adverse events | Baseline to End of Therapy +14 days | — |
| Dalbavancin Plasma Concentration | Day 1, Day 2, Day 14, and if applicable, Day 2, Day 28, Day 35 | Through level, mg/l |
| Microbiome analysis | Baseline, Day 90 and 1 year | Shannon Diversity Index, 1-5 range, Generally, a higher score indicates a BETTER outcome |
| Cost of antibiotic therapy | Day 90 | — |
| Number of days of work disability | Day 90 | — |
| modified Rankin Scale (mRS) | Day 90 and 1 year | 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) |
| EQ-5D-5L index | Day 90 and 1 year | 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. |
| Reintegration to Normal Living Index (RNLI) | Day 90 and 1 year | 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 |
Countries
Germany
Contacts
CONTACTStefan Hagel, PD Dr.
Outcome results
None listed