PT - JOURNAL ARTICLE AU - Oriol Sibila AU - Elena Laserna AU - Amelia Shoemark AU - Diana Bilton AU - Megan L Crichton AU - Anthony De Soyza AU - Wim G Boersma AU - Josje Altenburg AU - James D Chalmers TI - Heterogeneity of treatment response in bronchiectasis clinical trials AID - 10.1183/13993003.congress-2020.3332 DP - 2020 Sep 07 TA - European Respiratory Journal PG - 3332 VI - 56 IP - suppl 64 4099 - http://erj.ersjournals.com/content/56/suppl_64/3332.short 4100 - http://erj.ersjournals.com/content/56/suppl_64/3332.full SO - Eur Respir J2020 Sep 07; 56 AB - Introduction: Recent randomized clinical trials (RCTs) in bronchiectasis have failed to reach primary endpoints, suggesting a need to reassess how we measure treatment response. We aimed to determine patterns of response to treatment in bronchiectasis RCT and to study a new composite endpointMethods: We evaluated treatment response in 3 RCTs that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by change in the outcomes greater than the minimum clinically important difference (MCID). The composite endpoint was defined by one of 1) absence of exacerbation during follow-up, 2) improvement in quality of life (QOL) above the MCID and 3) improvement of FEV1 of ≥100ml.Results: Cumulatively the three studies included 984 patients. Response to treatment was heterogeneous in all trials. Improvement in QOL was not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r=-0.17, p=0.1 and r=0.04, p=0.4) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). Using the primary endpoints only the azithromycin trial showed a statistically significant difference versus placebo. Using a composite endpoint of clinical response, 82% of the patients receiving mannitol were responders vs 69% receiving placebo (p=0.002) and 81% of patients receiving azithromycin were responders vs 53% receiving placebo (p=0.01).Conclusions: Patients with bronchiectasis respond to drugs in different ways indicating that single endpoints do not measure the totality of treatment response. The use of a composite endpoint increases the precision of measuring treatment benefit in bronchiectasis clinical trials.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3332.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).