TY - JOUR T1 - Testing the effects of combining azithromycin with inhaled tobramycin for <em>P. aeruginosa</em> in cystic fibrosis: a randomised, controlled clinical trial JF - Thorax JO - Thorax SP - 581 LP - 588 DO - 10.1136/thoraxjnl-2021-217782 VL - 77 IS - 6 AU - David P Nichols AU - Pradeep K Singh AU - Arthur Baines AU - Lindsay J Caverly AU - James F Chmiel AU - Ronald L GIbson AU - Jorge Lascano AU - Sarah J Morgan AU - George Retsch-Bogart AU - Lisa Saiman AU - Hossein Sadeghi AU - Joanne L Billings AU - Sonya L Heltshe AU - Shannon Kirby AU - Ada Kong AU - Jerry A Nick AU - Nicole Mayer-Hamblett A2 - , Y1 - 2022/06/01 UR - http://thorax.bmj.com/content/77/6/581.abstract N2 - 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 (https://grants.nih.gov/grants/policy/data_sharing/). 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. ER -