Early Oral Switch Versus Intravenous Antibiotics in Previously Healthy Children and Adolescents With Bloodstream Infections
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 试验地点
- 18
- 主要终点
- Number of Participants with Treatment Failure
研究概览
简要总结
This nationwide, multicenter, randomized, non-inferiority trial of children and adolescents with uncomplicated bloodstream infections aims to investigate if early-oral antibiotic switch (experimental arm) is non-inferior to standard intravenous antibiotics (control arm) with respect to treatment failure.
详细描述
Background:
Bloodstream infections are among the leading causes of hospital admission and prolonged intravenous (IV) antibiotic therapy in children and adolescents. Current international guidelines recommend IV-only or prolonged IV antibiotic therapy before an oral switch (1,2), but these recommendations rely primarily on historical convention and low-quality evidence rather than randomized controlled trials (RCTs) (1,2). Both adult and pediatric studies suggest that shorter IV courses followed by oral step-down therapy may be safe and effective across a range of serious infections. However, no RCT has explicitly investigated early oral switch in previously healthy children with bloodstream infections.
Objective:
The trial objective is to determine whether early IV-to-oral antibiotic switch, once clinically stable, is non-inferior to continued standard IV therapy with respect to treatment failure in previously healthy children and adolescents aged 4 weeks to 17 years with bloodstream infections.
Study design:
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 4 Weeks 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 4 weeks to 17 years
- •Positive blood culture with a i) pathogenic bacterium (eg, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterobacterales, Fusobacterium spp. and other pathogenic bacteria) or ii) preliminary blood culture result (eg, Gram-negative rods or Gram-positive cocci in clusters/chains) judged by the investigator to be clinically relevant (ie, not a contaminant) and for which IV antibiotic therapy would be indicated according to standard guidelines
- •Clinical stability, defined as: (a) respiratory and haemodynamic stability, without need for oxygen, IV fluid therapy or inotropic support; and (b) well-appearing with signs of clinical improvement (eg, improved physical activity), as judged by the investigator
- •Tolerating oral fluids and diet, as judged by the investigator
- •Within the randomization window (see below)
- •Informed consent obtained from a parent or guardian, and from the patient if aged 15 years or older
- •Randomization window:
- •Randomization will take place (1) as soon as possible after eligibility is confirmed, and (2) before completion of a maximum of 4 days (96 hours) of effective IV antibiotic therapy, including the duration of the last IV dose (eg, 8 hours for penicillin and 24 hours for ceftriaxone)
排除标准
- •Complicated infections: a. Suspicion of endocarditis (echocardiography not performed routinely), b. Suspicion of CNS infection or post-septal cellulitis, c. Foreign material (eg, bone infection involving prosthetic material). d. Complicated postoperative course (eg, perforated appendicitis)
- •Blood culture positive with a. Neisseria meningitidis, b. Streptococcus pneumoniae if afebrile within 24 hours of blood culture collection, c. bacteria considered possible contaminants (eg, coagulase-negative staphylococci, Corynebacterium spp., Micrococcus spp.)
- •Premature infants with a corrected age of less than 28 days
- •No available suitable oral antibiotic (eg, due to antimicrobial resistance or contraindications)
- •Known chronic disease associated with an increased risk of severe infection: i) Immunosuppression, e.g., chemotherapy or biological therapy predisposing to severe infections, ii) Permanent central venous catheter due to an underlying condition, iii) Severe urinary tract abnormalities predisposing to bacteremia, including children receiving prophylactic antibiotic treatment.
研究组 & 干预措施
Early Oral Switch
Early Oral Switch
干预措施: Oral antibiotic therapy (Drug)
Standard Intravenous Therapy
Standard Intravenous Therapy
干预措施: Standard IV antibiotic therapy (Drug)
结局指标
主要结局
Number of Participants with Treatment Failure
时间窗: Within 8 weeks of randomization
Treatment failure, defined as clinically and/or microbiologically confirmed disease progression or relapse, adjudicated by an independent, blinded adjudication committee.
次要结局
- Intravenous Antibiotic Treatment Duration(Within 8 weeks of randomization)
研究者
Ulrikka Nygaard
Professor, senior consultant, MD, PhD
Rigshospitalet, Denmark