A randomized, open-label, single-visit crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD

Job van der Palen,1,2 Wendy Moeskops-van Beurden,1 Carolyn M Dawson,3 Wai-Yee James,3 Andrew Preece,4 Dawn Midwinter,4 Neil Barnes,5 Raj Sharma6 1Department of Pulmonology, Medisch Spectrum Twente, Enschede, the Netherlands; 2Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands; 3William Harvey Heart Centre, St Bartholomew Hospital, London, UK; 4Respiratory Therapy Area Unit, GlaxoSmithKline, Stockley Park, UK; 5Medical Department, GlaxoSmithKline, Brentford, UK; 6Respiratory Medical Franchise, GlaxoSmithKline, Brentford, UK Background: Administering maintenance COPD therapy with a combination of multiple inhalers may increase inhaler errors. This study evaluated the potential benefits of using a single Ellipta dry powder inhaler (DPI) compared with two combinations of DPIs commonly used to deliver triple maintenance therapy.Methods: Patients receiving inhaled COPD medication were enrolled in this multicenter, randomized, open-label, placebo-device, crossover study with a 2×2 complete block design (NCT0298218), which comprised two substudies: Ellipta vs Diskus + HandiHaler (substudy 1) or Turbuhaler + HandiHaler (substudy 2). Patients demonstrated inhaler use after reading the relevant patient information leaflet (PIL). A trained investigator assessed user errors (critical errors [errors likely to result in no or significantly reduced medication being inhaled] and overall errors). The primary endpoint was the proportion of patients making ≥1 critical error after reading the PIL. The secondary endpoints included error rates during ≤2 reassessments following investigator instruction (if required), instruction time, and patient preference.Results: After reading the PIL, significantly fewer patients made critical errors with Ellipta compared with Diskus + HandiHaler (9% [7/80] vs 75% [60/80], respectively; P<0.001) or Turbuhaler + HandiHaler (9% [7/79] vs 73% [58/79], respectively; P<0.001). The number of patients making overall errors was also lower with Ellipta vs tested inhaler combinations (P<0.001 for each substudy). The median instruction time needed for error-free use was shorter with Ellipta in substudies 1 and 2 (2.7 and 2.6 minutes, respectively) vs either combination (10.6 [Diskus + HandiHaler] and 11.3 minutes [Turbuhaler + HandiHaler], respectively). Significantly more patients preferred Ellipta over Diskus + HandiHaler or Turbuhaler + HandiHaler overall for taking their COPD medication (81% vs 9% and 84% vs 4%, respectively) and per the number of steps for taking their COPD medication (89% vs 8% and 91% vs 5%, respectively).Conclusion: Fewer patients with COPD made critical errors with the single DPI, and patients required less instruction time, compared with each dual DPI combination. Keywords: COPD, triple therapy, instruction, patient preference, inhaler technique, critical error