Dalbavancin Therapy for Infective Endocarditis

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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)
• Препарат 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)

Первичные конечные точки

• Comparison of the Desirability of Outcome Ranking (DOOR) on Day 90 between patients treated with dalbavancin and those treated with standard therapy [Срок оценки: Day 90]

Вторичные конечные точки (12)

• Length of hospital stay (days) [Срок оценки: Day 90]
• National Institutes of Health Stroke Scale (NIHSS) [Срок оценки: Day 90 and 1 year]
• PROMIS-29 domain-specific T-scores and pain intensity [Срок оценки: Day 90 and 1 year]
• Overall mortality [Срок оценки: Day 90 and 1 year]
• Cardiac surgery [Срок оценки: Day 90 and 1 year]
• Infectious complications [Срок оценки: Day 90 and 1 year]
• Embolic event [Срок оценки: Day 90 and 1 year]
• Clinical Frailty Scale [Срок оценки: Day 90 and 1 year]
• Occurrence of treatment-related adverse events [Срок оценки: Baseline to End of Therapy +14 days]
• Dalbavancin Plasma Concentration [Срок оценки: Day 1, Day 2, Day 14, and if applicable, Day 2, Day 28, Day 35]
• Microbiome analysis [Срок оценки: Baseline, Day 90 and 1 year]
• Cost of antibiotic therapy [Срок оценки: Day 90]

Критерии участия

Критерии включения

• ≥ 18 years
• written informed consent
• 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.

Критерии исключения

• Hemodynamic instability requiring vasopressor therapy within the last 72 hours prior to randomization
• Body temperature ≥38.0°C within the 72 hours prior to randomization
• Evidence of pathogen growth in a blood culture within the 72 hours prior to randomization
• Presence of a cardiac abscess at the time of randomization
• 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
• Duration of effective intravenous antibiotic therapy for endocarditis of < 7 days prior to randomization
• 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)
• Hypersensitivity to dalbavancin, vancomycin, teicoplanin, or other components of the investigational drug
• 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
• Continuous renal replacement therapy (e.g., CVVHD, CVVHDF)
• Child B or C liver cirrhosis
• Palliative care
• Secondary infections requiring a longer course of antibiotic therapy than that intended for the treatment of endocarditis
• Oral antibiotic therapy already initiated to treat the current episode of endocarditis
• Scheduled cardiac surgery after randomization, within the period designated for antibiotic treatment of endocarditis
• Intraspinal or brain abscess (> 0.5 cm)
• Pregnant and breastfeeding women
• Women of childbearing potential, unless the following criteria are met:

• Postmenopausal (12 months of natural amenorrhea or 6 months of amenorrhea with serum FSH > 40 mIU/mL)
• Postoperative (6 weeks after bilateral oophorectomy with or without hysterectomy)
• 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)
• sexual abstinence
• Vasectomy of the partner

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 9 центров

• Universitätsklinikum Freiburg — Freiburg im Breisgau
• Universitätsklinikum Regensburg — Regensburg
• Universitätsklinikum Hamburg-Eppendorf — Hamburg
• Universitätsklinikum Köln — Cologne
• Klinikum St. Gerog gGmbh — Leipzig
• Vivantes Auguste-Viktoria-Klinikum — Berlin
• Deutsches Herzzentrum der Charité (DHZC) — Berlin
• Helios Klinikum Erfurt GmbH — Erfurt
• … и ещё 1 центр

Идентификаторы

NCT: NCT07699211 · ZKSJ0165 · 2026-526149-91-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗