EPIC - 001, CLINICAL TRIAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项多中心随机临床试验，评估在囊性纤维化幼儿新发Pa阳性口咽、痰或下呼吸道培养时使用抗菌药物治疗的临床和微生物学疗效和安全性。大约300名参与者将被随机分配到两种早期抗假单胞菌治疗算法（循环或基于培养的治疗）中的一种。所有参与者将接受抗假单胞菌抗生素治疗的初始疗程，包括28天的吸入妥布霉素溶液和14天的口服环丙沙星/安慰剂疗程，无论随机分配如何。如果在第一个抗假单胞菌周期的三周后取样的呼吸培养物仍然呈阳性，参与者将接受额外的28天TSI疗程。在研究的剩余时间里，参与者将根据他们的随机分配进行如下治疗：循环治疗（n=150）： a.第一组（n=75）： TSI和口服安慰剂连续六个季度周期b.第二组（n=75）： TSI和口服环丙沙星联合治疗连续六个季度周期。基于培养的治疗（n=150）： a.第一组（n=75）：仅当季度呼吸培养发现Pa阳性时才给予TSI和口服安慰剂。b. II组（n+75）：仅当季度呼吸培养发现Pa阳性时才给予TSI和口服环丙沙星联合治疗。主要目标包括：1)在18个月的研究期间，比较循环治疗与基于培养的治疗在需要静脉注射抗生素和/或住院治疗的首次肺恶化的时间；2)在18个月的研究期间，比较两个治疗组在呼吸培养中Pa阳性分离物的比例。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a multicenter randomized clinical trial assessing the clinical and microbiologic efficacy and safety of treatment with antimicrobial therapy at the time of new onset of Pa positive oropharyngeal, sputum or lower respiratory tract culture in young children with cystic fibrosis. Approximately three hundred participants will be randomized to one of two early anti-pseudomonal treatment algorithms (CYCLED or CULTURE-BASED THERAPY). All participants will receive an initial course of anti-pseudomonal antibiotic therapy consisting of 28 days of tobramycin solution for inhalation and a 14-day course of oral ciprofloxacin/placebo regardless of randomization assignment. If respiratory cultures sampled after three weeks of the first anti-pseudomonal cycle remains positive, participants will receive an additional 28-day course of TSI. During the remainder of the study, participants will be treated based on their randomization assignment as follows: CYCLED Therapy (n=150): a. Group I (n=75): TSI and oral placebo for six consecutive quarterly cycles b. Group II (n=75): combination therapy of TSI and oral ciprofloxacin for six consecutive quarterly cycles. CULTURE-BASED Therapy (n=150): a. Group I (n=75): TSI and oral placebo administered only when quarterly respiratory cultures are found positive for Pa. b. Group II (n+75): combination therapy of TSI and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pa. Primary objectives include 1) Comparison of CYCLED Therapy to CULTURED-BASED Therapy on time to first pulmonary exacerbation requiring intravenous antibiotics and/or hospitalization during an 18-month study period and 2) compare the two treatment groups on the proportion of Pa positive isolates from respiratory cultures during an 18-month study period.