A Protocol of a Randomised, Two-arm Superiority Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Proportion of patients achieving PK/PD index: 100% fT>MIC (Ctrough >MIC)
研究概览
简要总结
The goal of this clinical trial is to examine the success and safety of administering certain antibiotics (beta-lactams) given in a longer 3-hour infusion to children (0-17 years) who are critically ill and have severe infection.
The main question it aims to answer is:
Is the longer infusion more effective than the conventional short-term (0.5-hour-long) infusion? Researchers will compare the 3-hour-long infusion group to the 0.5-hour-long infusion group to determine whether the longer infusion can cure the infection earlier and whether it is equally safe. The doses are the same in the two groups. Only the duration differs until the patient receives the antibiotic.
Participants will:
- be given the required antibiotic drug in a 3-hour-long or in a 0.5 hour-long infusion.
- be examined to make sure their blood drug levels are correct. This will require two blood tests.
- be treated according to routine care and have examinations and blood tests performed.
详细描述
Treatment begins with a short, intermittent infusion of antibiotics. If the patient meets study criteria, randomisation must occur within 24 hours. Prior to enrolment, written informed consent or a declaration of contribution must be signed by the legal guardian and, where age-appropriate, the patient.
Plans for the collection and laboratory evaluation of biological samples:
Per protocol:
This study involves collecting blood samples (200 µl per sample) to monitor drug levels, with each sample identified by the patient's assigned PIN (Personal Identification Number). To ensure measurements reflect steady-state conditions, samples must be collected at least 48 hours after the first post-allocation dose and immediately prior to the next scheduled dose (trough or minimum level). Analysis of free (unbound) drug concentrations is performed via High-Performance Liquid Chromatography (HPLC) with specific absorbance detection for meropenem (290 nm), piperacillin (252 nm), tazobactam (210 nm), and cefepime (263 nm); ceftriaxone is measured using Liquid Chromatography-Mass Spectrometry (LC-MS).
For evaluating the drug levels:
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
- 0 Hours 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •paediatric patients (0-17 years of age) with suspected or confirmed bacterial infection who are treated in a PICU or NICU and diagnosed with sepsis with a total Phoenix Sepsis Score ≥2 points, and the infection is clinically probable or confirmed by microbiological culture (e.g. from a blood culture, cerebrospinal fluid, urine, trachea, wound, etc.), excluding contamination;
- •who are receiving β-lactams including meropenem, piperacillin/tazobactam, cefepime and ceftriaxone;
- •who received the same β-lactam therapy within 24 hours prior to inclusion or started new β-lactam therapy due to clinical deterioration;
- •written consent of the parent or guardian is obtained.
排除标准
- •palliative care patients;
- •patients participating in other drug trials;
- •patients with impaired renal function if dosing modification is required (estimated Glomerular Filtration Rate [eGFR]<50 mL/min/1.73m2 for meropenem, cefepime, and piperacillin/tazobactam; eGFR<10 mL/min/1.73m2 for ceftriaxone);
- •patients undergoing plasmapheresis (TPE);
- •patients undergoing extracorporeal therapy (continuous kidney replacement therapy [CKRT] or extracorporeal membrane oxygenation [ECMO]);
- •β-lactam allergy;
- •patients admitted from another institution or department who have been on the same β-lactam treatment for more than 24 hours;
- •pregnancy.
研究组 & 干预措施
pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Short-term infusion time of the following beta-lactam: meropenem (Drug)
pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Short-term infusion time of the following beta-lactam: piperacillin/tazobactam (Drug)
pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Short-term infusion time of the following beta-lactam: cefepime (Drug)
pediatric patients, short-term infusion (P, SI) and neonatal patients, short-term infusion (N, SI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Short-term infusion time of the following beta-lactam: ceftriaxone (Drug)
pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Extended infusion time of the following beta-lactam: meropenem (Drug)
pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Extended infusion time of the following beta-lactam: piperacillin/tazobactam (Drug)
pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Extended infusion time of the following beta-lactam: cefepime (Drug)
pediatric patients, extended infusion (P, EI) and neonatal patients, extended infusion (N, EI)
subset P: 28 days - 17 years subset N: term or pre-term infants < 28 days of post-natal age, or PMA* < 44 weeks
*postmenstrual age
干预措施: Extended infusion time of the following beta-lactam: ceftriaxone (Drug)
结局指标
主要结局
Proportion of patients achieving PK/PD index: 100% fT>MIC (Ctrough >MIC)
时间窗: two times >48 hours after initiation of antibiotic treatment according to the treatment allocation
In critically ill patients, it is recommended to maintain plasma levels 1-4 times higher than the minimal inhibitory concentration (MIC) of the bacterium isolated throughout the dosing interval (100% fT\>1-4×MIC). The primary outcome for the study will be the proportion of patients achieving therapeutic and optimal drug exposure, defined as plasma concentrations above the MIC for 100% of the dosing interval. Trough plasma concentration levels should be measured. The pharmacokinetic-pharmacodynamic (PK/PD) index used is 100% fT\>MIC (Ctrough \>MIC).
次要结局
- Length of PICU/NICU stay in hours(From enrollment to the end of treatment (maximum 30 days).)
- Proportion of patients achieving PK/PD index: 100% fT>4xMIC (Ctrough >4xMIC)(two times >48 hours after initiation of antibiotic treatment according to the treatment allocation)
- Time to normalisation of C-reactive protein (CRP)(From enrollment to the end of treatment (maximum 30 days).)
- Time to normalisation of procalcitonin (PCT)(From enrollment to the end of treatment (maximum 30 days).)
- Duration of the antibiotic therapy(From enrollment to the end of treatment (maximum 30 days).)
- Time to normalisation of white blood cells (WBC)(From enrollment to the end of treatment (maximum 30 days).)
- Microbiological eradication rate(On day 0 before initiation of antibiotic treatment and on days 2, 3 and 5 after initiation of antibiotic treatment)
- Clinical response(Each day from enrollment to the end of treatment (maximum 30 days).)
- Time to clinical success or resolution(From enrollment to the end of treatment (maximum 30 days).)
- Treatment failure(From enrollment to the end of treatment (maximum 30 days).)
- Length of hospital stay (LOS) in days(From enrollment to the end of treatment (maximum 30 days).)
- All-cause mortality(From enrollment to the end of treatment (maximum 30 days).)
- Adverse events (AEs)(Each day from enrollment to the end of treatment (maximum 30 days).)