Procalcitonin to Reduce Antibiotic Use in Pediatric Pneumonia (P-RAPP)

降钙素原可减少小儿肺炎中抗生素的使用 (P-RAPP)

• 批准号: 10041764
• 负责人: Todd Adam Florin
• 金额: $ 39.69万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041764
• 关键词: Address; Adult; Adverse drug effect; Adverse effects; Adverse event; Algorithms; Amoxicillin; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Biological Markers; Blood; Characteristics; Child; Childhood; Clinical; Clinical Trials; Clostridium difficile; Colitis; Communities; Data; Detection; Development; Diagnosis; Diarrhea; Emergency Medicine; Enrollment; Feasibility Studies; Follow-Up Studies; Future; Goals; Guidelines; Health; High Prevalence; Hospitalized Child; Individual; Infection; Intervention; Interview; Methodology; Nature; Outcome; Outcome Study; Outpatients; Parents; Patients; Pilot Projects; Placebos; Pneumonia; Polymerase Chain Reaction; Predictive Value; Procedures; Publishing; Quality of life; Randomized; Recommendation; Reference Standards; Research; Research Design; Resolution; Risk; Safety; Sepsis; Site; Structure; Symptoms; Technology; Testing; Time; Training; Vaccines; Viral Pneumonia; Virus; Virus Diseases; Work; adherence rate; burden of illness; clinical efficacy; clinical risk; feasibility trial; improved; innovation; instrument; multidisciplinary; pediatric emergency; phase III trial; pilot trial; procalcitonin; randomized placebo controlled trial; randomized trial; response; side effect; standard care; study population; success; treatment strategy

PROJECT SUMMARY/ABSTRACT Although viruses are the leading cause of community-acquired pneumonia (CAP) in young children, antibiotics are prescribed for most children with CAP. Antibiotic overuse has substantial societal and individual consequences, including promotion of antimicrobial resistance, antibiotic-associated side effects and severe complications. Procalcitonin (PCT) is a biomarker that is increased in patients with bacterial infections but is not typically elevated in viral infections. A low PCT level has been shown to have a high negative predictive value for detection of typical bacteria in children with CAP. Similarly, PCT algorithms have decreased antibiotic use without increasing adverse events in adults and children; however, clinicians may be hesitant to use PCT, as the clinical efficacy of avoiding antibiotics in outpatient children with low-risk clinical characteristics and low PCT levels has not been evaluated. The overall objective of this work is to test the hypothesis that low-risk children managed as outpatients with CAP and PCT levels <0.25 ng/mL treated with placebo have similar clinical response to those treated with antibiotics, with fewer adverse effects, through a large-scale, multi- institutional randomized trial (RCT). Given the complexities of conducting an RCT of this nature, the overall objective of this R34 is to evaluate and finalize the study population, trial procedures and study outcomes necessary for the development of this future RCT, while assessing study feasibility through a pilot trial. Specific Aim 1 is to refine and finalize the study population, outcomes, procedures, instruments and training materials for a trial examining the need for antibiotics in low-risk children with CAP. As parent and clinician input is critical to the success of a “no antibiotics” strategy, we will perform qualitative semi-structured interviews with key stakeholders and use Delphi methodology with a panel of pediatric CAP experts to refine and finalize the study population, procedures and outcomes. We will also evaluate the reliability and feasibility of using mobile video chat technology to evaluate the clinical response of children with CAP, which we will leverage in the future RCT. Specific Aim 2 is to implement and establish feasibility of all study procedures by conducting a 3-site pilot trial of amoxicillin vs placebo in low-risk children with CAP and PCT levels <0.25 ng/mL. We will enroll and randomize 36 children at 3 participating sites. This pilot trial will provide necessary data to plan the large-scale definitive trial, including assessment of facilitators and barriers of study participation, estimating enrollment and attrition rates, evaluating study procedures and interventions in a real- world setting, and determining adherence rates. In addition, we will demonstrate the ability to collect outcomes important to the future RCT, including clinical response, symptom resolution, adverse events and quality of life. The subsequent large RCT will be significant, as it will definitively address whether antibiotics are beneficial in low-risk children with CAP, representing an innovative departure from the status quo by shifting from empirical antibiotic use for all children with CAP to a targeted approach.

项目总结/摘要 虽然病毒是幼儿社区获得性肺炎（CAP）的主要原因，但抗生素 是为大多数CAP患儿开的处方。抗生素过度使用对社会和个人 后果，包括促进抗菌素耐药性，药物相关的副作用和严重的 并发症降钙素原（PCT）是一种生物标志物，在细菌感染患者中增加，但在 在病毒感染中一般不会升高低PCT水平已被证明具有高阴性预测 对CAP患儿典型菌群的检测有重要价值。同样，PCT算法减少了抗生素 使用PCT不会增加成人和儿童的不良事件;然而，临床医生可能对使用PCT犹豫不决， 由于门诊患儿的临床疗效低危，避免使用抗生素， 尚未评价PCT水平。这项工作的总体目标是测试假设，即低风险 CAP和PCT水平<0.25 ng/mL的门诊患者接受安慰剂治疗的儿童， 临床反应，以那些与抗生素治疗，副作用少，通过大规模，多， 机构随机试验（RCT）。考虑到开展此类RCT的复杂性， 本R34的目的是评价并最终确定研究人群、试验程序和研究结局 在通过试点试验评估研究可行性的同时， 具体目标1是完善并最终确定研究人群、结局、程序、工具和培训 研究低危CAP儿童抗生素需求的试验材料。作为家长和临床医生 输入是成功的“无抗生素”战略的关键，我们将进行定性半结构化 与关键利益相关者进行访谈，并与儿科CAP专家小组一起使用德尔菲方法， 并最终确定研究人群、程序和结果。我们还将评估其可靠性和可行性 使用移动的视频聊天技术来评估CAP儿童的临床反应，我们将 在未来的RCT中发挥作用。具体目标2是通过以下方式实施并确定所有研究程序的可行性： 在CAP和PCT水平<0.25的低风险儿童中进行阿莫西林与安慰剂的3中心试点试验 ng/mL。我们将在3个参与研究中心入组并随机分配36名儿童。这项试点试验将提供必要的 计划大规模确定性试验的数据，包括评估研究的促进因素和障碍 参与，估计入组率和流失率，评价研究程序和干预措施，在一个真实的- 世界设置，并确定遵守率。此外，我们将展示收集结果的能力 对未来RCT很重要，包括临床反应、症状缓解、不良事件和生活质量。 随后的大型随机对照试验将具有重要意义，因为它将明确说明抗生素是否有益于 低风险儿童与CAP，代表了一个创新的偏离现状，从经验 抗生素的使用，所有儿童与CAP的目标的做法。