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, Wendy Moeskops-van Beurden, Carolyn M Dawson, Wai-Yee James, Andrew Preece, Dawn Midwinter, Neil Barnes, Raj Sharma, Job van der Palen, Wendy Moeskops-van Beurden, Carolyn M Dawson, Wai-Yee James, Andrew Preece, Dawn Midwinter, Neil Barnes, Raj Sharma

Abstract

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; critical errors; inhaler technique; instruction; patient preference; triple therapy.

Conflict of interest statement

Disclosure AP, RS, DM, and NB are employees of GSK and hold stocks and/or shares. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Proportion of patients with at least one critical inhaler error in substudy 1 (Ellipta vs Diskus + HandiHaler) and substudy 2 (Ellipta vs Turbuhaler + HandiHaler) after reading the PIL (ITT population). Notes: *Odds ratio: 29.114 (95% CI: 11.047, ∞). **Odds ratio: 27.744 (95% CI: 10.512, ∞). Abbreviations: ITT, intent to treat; PIL, patient information leaflet.
Figure 2
Figure 2
Kaplan–Meier plot of total time taken to demonstrate correct inhaler use. Notes: (A) Substudy 1: Ellipta vs Diskus + HandiHaler. (B) Substudy 2: Ellipta vs Turbuhaler + HandiHaler.

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