Rationale Inhaled tobramycin and oral azithromycin are common chronic therapies in people with cystic fibrosis and Pseudomonas aeruginosa airway infection. Some studies have shown that azithromycin can reduce the ability of tobramycin to kill P. aeruginosa . This trial was done to test the effects of combining azithromycin with inhaled tobramycin on clinical and microbiological outcomes in people already using inhaled tobramycin. We theorised that those randomised to placebo (no azithromycin) would have greater improvement in forced expiratory volume in one second (FEV1) and greater reduction in P. aeruginosa sputum in response to tobramycin. Methods A 6-week prospective, randomised, placebo-controlled, double-blind trial testing oral azithromycin versus placebo combined with clinically prescribed inhaled tobramycin in individuals with cystic fibrosis and P. aeruginosa airway infection. Results Over a 6-week period, including 4 weeks of inhaled tobramycin, the relative change in FEV1 did not statistically significantly differ between groups (azithromycin (n=56) minus placebo (n=52) difference: 3.44%; 95% CI: −0.48 to 7.35; p=0.085). Differences in secondary clinical outcomes, including patient-reported symptom scores, weight and need for additional antibiotics, did not significantly differ. Among the 29 azithromycin and 35 placebo participants providing paired sputum samples, the 6-week change in P. aeruginosa density differed in favour of the placebo group (difference: 0.75 log10 CFU/mL; 95% CI: 0.03 to 1.47; p=0.043). Conclusions Despite having greater reduction in P. aeruginosa density in participants able to provide sputum samples, participants randomised to placebo with inhaled tobramycin did not experience significantly greater improvements in lung function or other clinical outcomes compared with those randomised to azithromycin with tobramycin. Data are available upon reasonable request. At the time of publication of study findings, accrued data will be made available for sharing with other investigators at academic or non-profit institutions according to NIH data sharing policies (). Since original datasets will include sensitive information, including locations and dates of treatment, these data sets will be limited and will omit individual identifiers as per the Federal Health Insurance Portability and Accountability Act (HIPAA). Our foremost concern is protecting the rights and privacy of the persons volunteering to participate in our research studies. Data will be shared upon request with other investigators so long as the request conforms to the purposes specified in the consent form. In our consent form, we have specified that 'the data may be shared with other researchers and used in future research' and that 'the goal of future studies would be to help us understand cystic fibrosis better'. If the purpose intended by the data requestors is not clearly understood as specified in the consent form, the IRB will determine if additional consent is required. Investigators requesting data must sign a data-sharing agreement committing to: (1) using the data only for research purposes and not identifying any individual participant; (2) securing the data using appropriate computer technology; (3) not sharing the data with third parties and (4) destroying the data after analyses are completed. In addition to sharing the data, we will share a data dictionary, our standard documentation, so that the data will be as usable as practically possible. The Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Centre (CFF TDNCC) Data Archive has a documented process for requesting study data sponsored by the CFF and conducted by the CFF TDNCC. As a part of the process, investigators seeking data will apply, undergo scientific review, provide evidence of IRB approval for their proposed research and submit a data use agreement between their home institution and the TDNCC Data Archive.

中文翻译：

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测试阿奇霉素与吸入妥布霉素联合治疗铜绿假单胞菌对囊性纤维化的影响：一项随机对照临床试验

基本原理 吸入妥布霉素和口服阿奇霉素是囊性纤维化和铜绿假单胞菌气道感染患者的常见慢性疗法。一些研究表明，阿奇霉素可以降低妥布霉素杀灭铜绿假单胞菌的能力。该试验的目的是测试阿奇霉素与吸入妥布霉素联合使用对已经使用吸入妥布霉素的患者的临床和微生物学结果的影响。我们推测，那些随机接受安慰剂（不含阿奇霉素）的患者在第一秒用力呼气量（FEV1）方面会有更大的改善，并且对妥布霉素的反应会更大程度地减少铜绿假单胞菌痰液。方法 在患有囊性纤维化和铜绿假单胞菌气道感染的个体中进行为期 6 周的前瞻性、随机、安慰剂对照、双盲试验，测试口服阿奇霉素与安慰剂联合临床处方吸入妥布霉素的情况。结果 在 6 周期间，包括 4 周吸入妥布霉素，各组之间 FEV1 的相对变化没有统计学显着差异（阿奇霉素 (n=56) 减去安慰剂 (n=52) 差异：3.44%；95% CI： −0.48 至 7.35；p=0.085）。次要临床结果的差异，包括患者报告的症状评分、体重和额外抗生素的需要，没有显着差异。在提供配对痰样本的 29 名阿奇霉素参与者和 35 名安慰剂参与者中，铜绿假单胞菌密度的 6 周变化有利于安慰剂组（差异：0.75 log10 CFU/mL；95% CI：0.03 至 1.47；p=0.043 ）。结论 尽管能够提供痰样本的参与者的铜绿假单胞菌密度有更大程度的降低，但与随机分配到阿奇霉素和妥布霉素的参与者相比，随机分配到安慰剂和吸入妥布霉素的参与者在肺功能或其他临床结果方面并未出现显着更大的改善。数据可根据合理要求提供。研究结果发表时，根据 NIH 数据共享政策，累积数据将与学术或非营利机构的其他研究人员共享（）。由于原始数据集将包含敏感信息，包括治疗地点和日期，因此这些数据集将受到限制，并且根据联邦健康保险流通和责任法案 (HIPAA)，将省略个人标识符。我们最关心的是保护自愿参与我们研究的人员的权利和隐私。只要请求符合同意书中指定的目的，数据将根据要求与其他研究人员共享。在我们的同意书中，我们明确指出“这些数据可能会与其他研究人员共享并用于未来的研究”，并且“未来研究的目标是帮助我们更好地了解囊性纤维化”。如果数据请求者的预期目的未按照同意书的规定明确理解，IRB 将决定是否需要额外同意。研究者索取数据必须签署数据共享协议，承诺： (1) 仅将数据用于研究目的，不识别任何个人参与者；(2) 使用适当的计算机技术保护数据；(3) 不与第三方共享数据；(4) 分析完成后销毁数据。除了共享数据之外，我们还将共享数据字典，即我们的标准文档，以便数据尽可能实用。囊性纤维化基金会治疗开发网络协调中心 (CFF TDNCC) 数据档案有一个记录的流程，用于请求由 CFF 赞助并由 CFF TDNCC 进行的研究数据。作为该过程的一部分，寻求数据的研究人员将提出申请，接受科学审查，提供 IRB 批准其拟议研究的证据，并提交其所在机构与 TDNCC 数据档案馆之间的数据使用协议。