Intravenous to Oral Antibiotic Switch Therapy for Probable Neonatal Bacterial Infections: Clinical Efficacy, Safety and Cost-effectiveness
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 510
- 试验地点
- 18
- 主要终点
- Bacterial re-infection within 28 days after cessation of antibiotic treatment (within 35 days after initial presentation)
研究概览
简要总结
Randomized controlled open-label non-inferiority trial comparing complete intravenous antibiotic treatment with a short iv. course followed by oral antibiotics in neonates (0-28 days) with probable bacterial infection.
Primary outcome:
- Bacterial re-infection within 28 days after finishing of antibacterial therapy.
Secondary outcome(s):
- Pharmacokinetic profile of oral amoxicillin/clavulanic acid
- Quality of life
- Cost-effectiveness
- Alterations in gut microbiome
- Use of molecular techniques for better detection of bacterial pathogens
详细描述
Neonates have a high antibiotic consumption because of their susceptibility for bacterial infections. Since the early diagnosis of bacterial infection in neonates is difficult, intravenous broad-spectrum antimicrobial therapy is usually started promptly after subtle symptoms. The majority of neonates become asymptomatic shortly after initiation; when infection is probable or proven by elevated inflammatory markers and/or a positive blood culture, intravenous antibiotics are administered for at least 7 days.
However, for neonates blood culture has a limited sensitivity. Therefore, the majority of neonates with probable infection are treated for a prolonged time with intravenous broad-spectrum antimicrobial therapy. In older children, intravenous antibiotics are often changed to oral antibiotics after cessation of symptoms and decreasing inflammatory parameters. This is not yet widely practised in neonates because of uncertainties in pharmacokinetics. Two explorative small studies from France and Italy into neonatal antibiotic switch therapy suggest that follow-up treatment with an oral antibiotic is promising; but the non-inferiority and safety was not yet properly addressed. Neonatal switch therapy, if proven to be safe and efficacious, would have a major impact on neonatal well-being, mother-to-child bonding and moreover costs.
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
- 1 Day 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonates (≥ 35+0 weeks, 0-28 days old, ≥ 2 kg)
- •Probable bacterial infection defined as clinical symptoms and/or maternal risk factors and elevated inflammatory markers for which empiric broad-spectrum antibiotic treatment was initiated and needs to be continued for > 48 hours
- •Clinically well
- •Toleration of oral feeding without overt vomiting
- •Signed informed consent
排除标准
- •Proven bloodstream infection
- •Absence of blood culture
- •Severe localized infection (meningitis, osteomyelitis, necrotizing enterocolitis)
- •Severe clinical sepsis (compromised circulation, need for mechanical ventilation)
- •Continuous need for a central venous line
- •Severe hyperbilirubinemia exceeding the exchange level
- •Parents inability to administer medication
- •Major congenital or syndromic anomalies
研究组 & 干预措施
Oral group
After 48 hours of intravenous antibiotics eligible neonates will switch to amoxicillin/clavulanic acid suspension for the remaining 5 days. When the oral suspension is well tolerated neonates can be discharged from hospital.
In order to investigate the pharmacokinetic profile of oral amoxicillin/clavulanic acid serum levels will be measured.
干预措施: Amoxicillin Clavulanate (Drug)
Intravenous group
Neonates will complete the full course of antibiotics of 7 days intravenously in hospital following local protocol.
干预措施: Antibiotics (Drug)
结局指标
主要结局
Bacterial re-infection within 28 days after cessation of antibiotic treatment (within 35 days after initial presentation)
时间窗: 0-35 days
次要结局
- Difference in Quality of Life between oral and intravenous antibiotic treatment(0-35 days after birth)
- Duration of hospitalization(0-35 days after birth)
- Percentage of re-admission(0-35 days after birth)
- Time above MIC (T>MIC) of oral amoxicillin.(0-7 days)
- Time above MIC (T>MIC) of oral clavulanic acid.(0-7 days)
- Total costs and cost-effectiveness(0-35 days after birth)
研究者
Gerdien Tramper
Principal investigator, MD, PhD
Franciscus Gasthuis