A Non-Interventional Study of Tiotropium/Olodaterol versus Any Triple Combination Therapy for Chronic Obstructive Pulmonary Disease: The EVELUT® Study Protocol

Abstract

Background: The Global Initiative for Chronic Obstructive Lung Disease 2020 report recommends that patients with chronic obstructive pulmonary disease (COPD) suffering from persistent dyspnea, despite long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance therapy, are switched to either a long-acting muscarinic antagonist (LAMA)/LABA combination regimen or LAMA/LABA/ICS triple therapy. However, to date, no studies have investigated the direct switch from LABA/ICS to LAMA/LABA therapy-instead of switching to triple therapy-in a prospective, real-world, non-interventional setting.

Methods: EVELUT® (NCT03954132) is an ongoing, prospective, open-label, multicenter, non-interventional study comparing the once-daily fixed-dose combination of tiotropium and olodaterol (tio/olo) versus any triple therapy (LAMA/LABA/ICS) in patients with COPD who are symptomatic despite LABA/ICS maintenance therapy. Patients with acute or frequent COPD exacerbations are excluded from the study. Participants will receive LABA/ICS maintenance treatment until Visit 1, followed by switching of treatment to tio/olo or LAMA/LABA/ICS. The primary endpoints are changes in modified Medical Research Council (mMRC) and COPD Assessment Test (CAT®) scores after approximately 12 weeks of treatment. Secondary endpoints are change in the patients' general condition according to the Physician's Global Evaluation score, the proportion of responders with a change in mMRC score of ≥1 and in CAT® score of ≥2, and patient satisfaction with the inhaler and therapy. The study is expected to enroll approximately 900 patients.

Conclusion: EVELUT results are expected to add to the current real-world evidence informing therapeutic decisions for COPD in everyday clinical practice.

Trial registration: The European Union electronic Register of Post-authorisation Studies (EU PAS Register): EUPAS29784; the Federal Institute for Drugs and Medical Devices (BfArM): NIS Study No 7305; Clinicaltrials.gov: NCT03954132.

Keywords: COPD; LAMA/LABA/ICS; Spiolto® Respimat®; tiotropium/olodaterol; triple therapy.

Conflict of interest statement

Roland Buhl reports grants and personal fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Roche, and personal fees from AstraZeneca, Chiesi, Cipla, Sanofi and Teva, outside the submitted work. Michael Dreher received speaking fees from Actelion, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Chiesi, Hamilton, Heinen und Löwenstein, Intermune, Linde, Novartis, Pfizer, Philips Respironics, ResMed, Roche, and Weinmann, and honoraria for advising from Almirall, Boehringer Ingelheim, Hamilton, Linde, Novartis, Pfizer, Philips Respironics, ResMed, and Roche; and grants from Linde, Philips Respironics, ResMed and the German Federal Ministry of Education and Research (BMBF). Stephanie Korn received personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Roche, Sanofi and Teva, outside the submitted work. Christian Taube reports no conflict of interest. Christian Stock, Christoph M. Zehendner and Anke Kondla are employees of Boehringer Ingelheim. Claus F Vogelmeier reports personal fees from Almirall, Cipla, Berlin Chemie/Menarini, CSL Behring and Teva; grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, MedUpdate, Mundipharma, Novartis, Nuvaira, OmniaMed, and Takeda; and grants from the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), Bayer Schering Pharma AG, MSD and Pfizer, outside the submitted work. The authors report no other conflicts of interest in this work.

© 2020 Buhl et al.

Figures

Figure 1

GOLD 2020 follow-up pharmacologic treatment recommendations.*Consider if eos ≥ 300 or eos ≥ 100 AND ≥ 2 moderate exacerbations/1 hospitalization. **Consider de-escalation of ICS or switch if pneumonia, inappropriate original indication or lack of response to ICS. ©2020, Global Initiative for Chronic Obstructive Lung Disease, reproduced with permission. Abbreviations: eos, blood eosinophil count; FEV1, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist.

Figure 2

EVELUT® study overview. Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; V, visit.