Randomized Open-label Controlled Trial Evaluating a Single-dose Intravenous Dalbavancin Versus Standard Antibiotic Therapy During Catheter-related Bloodstream Infections Due to Staphylococcus Aureus
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 406
- 试验地点
- 2
- 主要终点
- Cure rate
研究概览
简要总结
The primary objective of the study is to demonstrate, among patients with non-complicated CR-BSIs due to S. aureus, that a single-dose of intravenous (IV) dalbavancin 1500 mg is non-inferior to standard documented antibiotic therapy for 14 days according to national guidelines at DAY 30 (Long follow up visit).
As the secondary objectives, the study aims to evaluate according to treatment group:
- Cure rate at DAY 14 and DAY 90 (EOS);
- Mortality rate within 90 days of follow-up;
- Time to negativation of blood cultures;
- Patient's quality of life;
- Hospitalization length of stay;
- Cost-utility analyses;
- Occurrence of any adverse event (AE and SAE), until Day 90 (EOS).
详细描述
Catheter-related bloodstream infections (CR-BSIs) are the most common nosocomial bloodstream infections, with an incidence as high as 8.5 to 19.8 infections per 1000 catheter-days. Staphylococcus aureus is involved in about 20% of CR-BSIs and associated with significant morbidity, mortality (9.3%), prolonged hospital stay (+ 9 days), and healthcare costs (35 000 € to 65 000 € per case). S. aureus CR-BSIs occurs mainly in frail patients with a port of catheter for chemotherapy or parenteral nutrition.
According to international guidelines, management of CR-BSIs due to S. aureus includes the removal and replacement of the infected catheter and a 14-day intravenous (IV) antibiotic therapy. Therefore, the management of CR-BSIs due to S. aureus requires the insertion of a new intravenous catheter. In turn, the new catheter can also lead to new septic complications and limit the patients' autonomy. Non-adherence to these recommendations leads to over-mortality and costs.
Following of the positive results of the SABATO trial in 2021 to determine whether early switch to oral antibiotic therapy is safe and effective in patients with uncomplicated BSA, oral switch during staphylococcal bacteremia, will likely become the standard of care. It is therefore justified to allow oral switch in the control arm.
The usual practice in some centers is already to switch to oral antibiotics, after a minimum of 7 days of intravenous treatment.
Dalbavancin is a new glycopeptide antibiotic, with an excellent bactericidal activity against Gram-positive bacteria, especially S. aureus, and a prolonged half-life of 14 to 15 days. As a comparison, half-life of antibiotics usually used for CR-BSIs due to S. aureus, i.e. penicillin or glycopeptide, as-per sensitivity to methicillin is much lower: 1.5 to 9 hours. Such prolonged half-life allows one IV injection to be sufficient and effective over 14 days of treatment. This remarkable characteristic should allow patients to be promptly discharged from hospital without monitoring.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged at least 18 years;
- •Blood cultures positive for S. aureus, obtained within 72 hours before randomization (the date considered is the date of the sampling, not the results);
- •CR-BSI, defined as:
- •One positive blood culture AND Local signs of infection at the catheter site; OR
- •at least one positive blood culture obtained from the catheter and the peripheral vein; AND
- •A differential period between catheter versus peripheral blood culture positivity of at least 2h as recommended; AND
- •Same S. aureus isolate (same phenotype) identified from the catheter and the peripheral vein blood cultures; OR
- •One positive blood culture; AND
- •Strong presumption of catheter-related infection according to clinical opinion.
- •Intravascular catheter - implantable venous access device (port-a-cath and Piccline) - removed before randomization;
- •Informed consent form date and signed by the patient.
排除标准
- •Polymicrobial infection;
- •Dalbavancin resistant strain;
- •More than 72 hours of active antibiotic treatment targeting S. aureus (in-vitro susceptibility) administered prior to randomization;
- •Patient with known valvulopathy, previous history of endocarditis, or suspicion of infective endocarditis by physician in charge;
- •Suspicion of any other deep focus infections, such as arthritis, pneumonia, osteomyelitis, or meningitis, presence of cerebral or peripheral emboli (arterial occlusion);
- •Thrombophlebitis;
- •Failure to remove any intravascular catheter which was present when first positive blood culture;
- •Signs of infection associated with quick SOFA score ≥ 2 at randomization;
- •Patients with foreign bodies such as: prosthetic heart valve, endovascular prosthesis, ventriculo-atrial shunt, pacemaker, or an automated implantable cardioverter defibrillator (AICD) device;
- •Severe liver disease (Child-Pugh C);
- •Severely immunocompromised patients:
- •Neutropenia (< 500 neutrophils/µL) at randomization;
- •Hematopoietic stem cell transplantation within the past 6 months or planned during treatment period;
- •Solid organ transplant;
- •Contraindication to dalbavancin and/or glycopeptide;
- •Life expectancy < 3 months;
- •Active injection drug user;
- •Pregnant or breastfeeding women;
- •For premenopausal women: failure to use highly-effective contraceptive methods for 1 month after receiving study drug;
- •Participation in other interventional trials ongoing;
- •Persons held in an institution by legal or official order;
- •Patients under legal protection;
- •Patients under guardianship or curators;
- •Patients unable to give a free and informed consent;
- •Patient not affiliated to a social security scheme: obligation of affiliation to a social security scheme or to be a beneficiary.
研究组 & 干预措施
Dalbavancin
Dalbavancin (Xydalba®) 1500 mg - One unique dose
干预措施: Dalbavancin administration (Drug)
Standard documented antibiotic therapy for 14 days according to national guidelines.
As currently recommended, investigators will be encouraged to use the intravenous route for the entire duration of treatment. However, in order to interfere as little as possible with usual practice in each center, the antimicrobial therapy will be let to the choice of the physician in charge of the patient after a minimum of 7 days of intravenous treatment.
During all the duration of the study, in case of worsening of the clinical condition requiring the prescription of antistaphylococcal, the clinician will prescribe additional antibiotherapy according to standard good practice.
干预措施: Standard antibiotic therapy (Drug)
结局指标
主要结局
Cure rate
时间窗: DAY 30
Clinical cure without relapse, defined by the absence of all the following: * Local and/or general signs of infection: * Relapse of bacteremia to S. aureus - i.e. a bacteremia due to S. aureus occurring after initial negativation of blood cultures (2 vials); * In dalbavancin arm: Any additional antibiotic therapy active on S. aureus received between DAY 0 and DAY 14; * In both arms: Any additional antibiotic therapy active on S. aureus received after DAY 14; i.e. between DAY 14 and DAY 30; * Deep focus infection including endocarditis; * Death from all causes.
次要结局
- Mortality rate(DAY 90)
- Cure rate(DAY 14;DAY 90 (EOS))
- Bloodstream clearance(DAY 14)
- Patient's quality of life(BASELINE; DAY 14; DAY 30; DAY 90 (EOS))
- Cost-utility analyses(DAY 90)
- Incidence of any adverse event (AE and SAE)(DAY 90)
- Hospitalization length of stay(DAY 90)