TRONARTO: A Randomized, Placebo-Controlled Study of Tiotropium/Olodaterol Delivered via Soft Mist Inhaler in COPD Patients Stratified by Peak Inspiratory Flow

Abstract

Donald A Mahler,1,2 Andrea Ludwig-Sengpiel,3 Gary T Ferguson,4 Alberto de la Hoz,5 John Ritz,6 Asif Shaikh,7 Henrik Watz8 1Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 2Section of Pulmonary Medicine, Valley Regional Hospital, Claremont, NH, USA; 3KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany; 4Department of Medicine, Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 5Cardio-Metabolism and Respiratory, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 6Biostatistics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 7Clinical Development & Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 8Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, GermanyCorrespondence: Donald A MahlerMedicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USATel [phone]Fax [phone]Email [email protected]: Inhaled bronchodilator therapy is currently the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Some inhalers require patients to achieve certain inhalation efforts either to activate the device or to deliver medication to the site of action. For dry powder inhalers, low peak inspiratory flow (PIF) can result in poor medication delivery but the clinical significance of this is not well understood.Methods: TRONARTO was a 4-week, randomized, double-blind, placebo-controlled, multicenter, parallel-group study which stratified patients with moderate-to-severe COPD according to their PIF against medium-low resistance at screening. Patients were randomized to receive tiotropium/olodaterol (5 μg/5 μg) or matched placebo delivered via the Respimat® Soft Mist™ inhaler (SMI). After 4 weeks of treatment, we assessed change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0– 3 hours (FEV1 AUC0– 3h) and trough FEV1.Results: Overall, 213 patients were randomized, of whom 106 received tiotropium/olodaterol (PIF < 60 L/min, 55; PIF ≥ 60 L/min, 51) and 107 received placebo (PIF < 60 L/min, 55; PIF ≥ 60 L/min, 52). For FEV1 AUC0– 3h, the adjusted mean change from baseline versus placebo was 336 mL (95% confidence interval [CI] 246– 425 mL; P< 0.0001) in the PIF < 60 L/min group and 321 mL (95% CI 233– 409 mL; P< 0.0001) in the PIF ≥ 60 L/min group. For trough FEV1, the adjusted mean change from baseline versus placebo was 201 mL (95% CI 117– 286 mL; P< 0.0001) in the PIF < 60 L/min group and 217 mL (95% CI 135– 299 mL; P< 0.0001) in the PIF ≥ 60 L/min group.Conclusion: In the TRONARTO study, which included patients with moderate-to-severe COPD and varying inspiratory flow abilities, treatment with tiotropium/olodaterol resulted in significant lung function improvements versus placebo. This SMI can be used irrespective of the PIF that a patient can generate.Keywords: inhaler, tiotropium/olodaterol, peak inspiratory flow, SMI, lung function

Keywords

• inhaler
• tiotropium/olodaterol
• peak inspiratory flow
• smi
• lung function.