Short Course Versus Standard Course Antifungal Therapy for Pediatric Candidemia: A Multi-Center Randomized Controlled Trial

儿童念珠菌血症的短期疗程与标准疗程抗真菌治疗：一项多中心随机对照试验

• 批准号: 10487627
• 负责人: Brian T Fisher
• 金额: $ 146.86万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2029-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487627
• 关键词: Adult; Americas; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antifungal Therapy; Automobile Driving; Bacteremia; Bacterial Infections; Benefits and Risks; Biological Assay; Biological Markers; Blood; Candida; Candidiasis; Child; Childhood; Clinical; Cohort Studies; Communicable Diseases; Communities; Comparative Study; Complication; Data; Disease; Drug Interactions; Early Diagnosis; Effectiveness; Expert Opinion; Fluconazole; Foundations; Funding; Future; Guidelines; Human Resources; Infection; International; Knowledge; Laboratories; Lead; Length of Stay; Measures; Methodology; Molds; Morbidity - disease rate; Multicenter Studies; Mycoses; Observational Study; Otitis Media; Outcome; Outcome Measure; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pneumonia; Prospective Studies; Publishing; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recommendation; Research; Research Personnel; Resolution; Site; Societies; United States National Institutes of Health; Update; Urinary tract infection; Yeasts; arm; base; biomarker performance; candidemia; clinical epidemiology; comparative effectiveness study; design; effective therapy; improved; improved outcome; molecular marker; mortality; multidisciplinary; novel; novel marker; optimal treatments; prospective; randomized trial; rapid diagnosis; response; standard of care; therapy duration

Invasive candidiasis is the most common invasive fungal disease, and uncomplicated candidemia is the most common presentation. Randomized controlled trials in adults and a prospective observational study in children demonstrated primary treatment with an echinocandin antifungal improved outcomes. While these data inform initial therapy choice, there remains a paucity of data regarding appropriate duration of therapy. Current guidelines recommend 14 total days of antifungal therapy for candidemia regardless of clinical presentation and initial response, yet this is based on opinion and not comparative data. Several studies have proven that shorter durations of antibacterial therapy are safe and effective for the treatment of numerous serious bacterial infections. However, there has been no comparative study to assess shorter versus standard duration therapy for any invasive fungal disease. A large proportion of pediatric invasive candidiasis is uncomplicated candidemia with relatively rapid clinical improvement on primary echinocandin therapy. It is hypothesized that these patients do not require 14 days of therapy and instead would be effectively treated with a shorter duration. The primary objective of this randomized controlled trial is to determine whether 7 more days of therapy is necessary after completing an initial 7days of echinocandin therapy for pediatric candidemia. Subjects initially treated with an echinocandin showing clinical improvement with blood culture clearance will be randomized at 7 days into one of two arms: 1) cessation of therapy, or 2) continuation of therapy for 14 total days. This primary aim will include a novel outcome measure, the desirability of outcome ranking (DOOR), which simultaneously captures benefits and negative consequences of treatment. We will compare the DOOR outcome in children randomized to receive 7 days of an echinocandin only (short-course) versus 7 days of echinocandin therapy followed by 7 more days of antifungal therapy (standard-course). We hypothesize that subjects randomized to short-course therapy will on average have a higher DOOR measure than subjects randomized to standard-course therapy. The secondary objective will assess utility of a novel biomarker, the T2Candida® assay, to provide supporting evidence for effectiveness of short course therapy. We previously demonstrated the T2Candida® assay can rapidly diagnose invasive candidiasis in children. However, there are no data on the utility of a negative biomarker to support cessation of therapy. Aim 2 will compare the 14-day DOOR measure for subjects with a negative or positive T2Candida® biomarker at day 7 of therapy within each study group. We hypothesize that a negative T2Candida® biomarker at day 7 will be associated with a higher DOOR measure at day 14. This study will leverage the Pediatric Fungal Network (PFN), a multidisciplinary group composed of 37 sites across the US and the only such group dedicated to pediatric invasive fungal disease. This will be the first randomized controlled trial to define the optimal duration of therapy for any invasive fungal disease, and the first to explore the utility of a fungal biomarker to support a shorter course. Results could impact numerous national and international guidelines.

侵袭性念珠菌病是最常见的侵袭性真菌疾病，其中单纯念珠菌病最为常见