EPIC - 001, CLINICAL TRIAL

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项多中心随机临床试验，评估囊性纤维化幼儿在口咽、痰或下呼吸道培养新出现Pa阳性时抗菌治疗的临床和微生物学疗效和安全性。大约300名受试者将随机接受两种早期抗假单胞菌治疗方案（周期性或基于培养的治疗）之一。所有受试者将接受抗假单胞菌抗生素治疗的初始疗程，包括28天的妥布霉素吸入溶液和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采样的呼吸道培养物仍然呈阳性，则参与者将接受额外的28天TSI疗程。在研究的剩余部分期间，将基于参与者的随机分配对参与者进行如下治疗：组I（n=75）：TSI和口服安慰剂连续6个季度周期B。II组（n=75）：TSI和口服环丙沙星联合治疗， 连续六个季度周期。 基于培养的疗法（n=150）：a.组I（n=75）：仅当每季度呼吸道培养发现Pa阳性时给予TSI和口服安慰剂。 B.组II（n+75）：TSI和口服环丙沙星联合治疗，仅在每季度呼吸道培养发现Pa阳性时给予。 主要目的包括：1）在18个月研究期间，比较循环治疗与基于培养的治疗在至首次肺部急性加重（需要静脉注射抗生素和/或住院治疗）的时间方面的差异; 2）在18个月研究期间，比较两个治疗组在呼吸道培养物中Pa阳性分离株的比例方面的差异。

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.