The Tiotropium Safety and Performance in Respimat® (TIOSPIR®) Trial: Spirometry Outcomes

Antonio Anzueto, Robert Wise, Peter Calverley, Daniel Dusser, Wenbo Tang, Norbert Metzdorf, Ronald Dahl, Antonio Anzueto, Robert Wise, Peter Calverley, Daniel Dusser, Wenbo Tang, Norbert Metzdorf, Ronald Dahl

Abstract

Background: Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups.

Methods: TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial.

Results: The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: -10 [-38, 18] mL for Respimat® 5 μg and, -37 [-65, -9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not.

Conclusions: The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not. Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.

Trial registration: NCT01126437.

Figures

Fig. 1
Fig. 1
Trough forced expiratory volume in 1 second (FEV1) over time (a), and difference versus HandiHaler® 18 μg (b) [7]. Noninferiority was evaluated for treatment main effects using a noninferiority δ of 50 mL. Abbreviations: FEV1 = forced expiratory volume in 1 second
Fig. 2
Fig. 2
Trough forced vital capacity (FVC) over time (a), and difference versus HandiHaler® 18 μg (b). Abbreviations: FVC = forced vital capacity
Fig. 3
Fig. 3
Forest plot of annual rate of forced expiratory volume in 1 second (FEV1) decline in lung function by baseline characteristics. Abbreviations: BMI = body mass index; FEV1 = forced expiratory volume in 1 second; ICS = inhaled corticosteroid; LABA = long-acting β2-agonist; LAMA = long-acting muscarinic receptor antagonist

References

    1. Bateman E, Singh D, Smith D, Disse B, Towse L, Massey D, Blatchford J, Pavia D, Hodder R. Efficacy and safety of tiotropium Respimat SMI in COPD in two 1-year randomized studies. Int J Chron Obstruct Pulmon Dis. 2010;5:197–208.
    1. Bateman ED, Tashkin D, Siafakas N, Dahl R, Towse L, Massey D, Pavia D, Zhong NS. A one-year trial of tiotropium Respimat plus usual therapy in COPD patients. Respir Med. 2010;104:1460–1472. doi: 10.1016/j.rmed.2010.06.004.
    1. Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack RL, Menjoge SS, Serby CW, Witek T., Jr A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19:217–224. doi: 10.1183/09031936.02.00269802.
    1. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543–1554. doi: 10.1056/NEJMoa0805800.
    1. Summary of Product Characteristics: Spiriva Respimat. 2013.
    1. Wise RA, Anzueto A, Calverley P, Dahl R, Dusser D, Pledger G, Koenen-Bergmann M, Joseph E, Cotton D, Disse B. The Tiotropium Safety and Performance in Respimat Trial (TIOSPIR), a large scale, randomized, controlled, parallel-group trial-design and rationale. Respir Res. 2013;14:40. doi: 10.1186/1465-9921-14-40.
    1. Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, Dusser D, Joseph E, Kattenbeck S, Koenen-Bergmann M, et al. Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med. 2013;369:1491–1501. doi: 10.1056/NEJMoa1303342.
    1. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;16:5–40. doi: 10.1183/09041950.005s1693.
    1. Mallinckrod CH, Lane PW, Schnell D, Peng Y, Mancuso JP. Recommendations for the Primary Analysis of Continuous Endpoints in Longitudinal Clinical Trials. Drug Information Journal. 2008;42:303–319.
    1. Hvizdos KM, Goa KL. Tiotropium bromide. Drugs. 2002;62:1195–1203. doi: 10.2165/00003495-200262080-00008.
    1. Summary of Product Characteristics (SPC): Spiriva 18 microgram inhalation powder, hard capsule []
    1. Summary of Product Characteristics (SPC): Spiriva Respimat 2.5 microgram inhalation solution []
    1. Celli BR, Thomas NE, Anderson JA, Ferguson GT, Jenkins CR, Jones PW, Vestbo J, Knobil K, Yates JC, Calverley PM. Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med. 2008;178:332–338. doi: 10.1164/rccm.200712-1869OC.
    1. Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med. 2011;365:1184–1192. doi: 10.1056/NEJMoa1105482.
    1. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977;1:1645–1648. doi: 10.1136/bmj.1.6077.1645.
    1. Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:95–99. doi: 10.2147/COPD.S27480.
    1. Decramer M, Cooper CB. Treatment of COPD: the sooner the better? Thorax. 2010;65:837–841. doi: 10.1136/thx.2009.133355.
    1. Anzueto A, Tashkin D, Menjoge S, Kesten S. One-year analysis of longitudinal changes in spirometry in patients with COPD receiving tiotropium. Pulm Pharmacol Ther. 2005;18:75–81. doi: 10.1016/j.pupt.2004.10.003.
    1. Celli B, Decramer M, Kesten S, Liu D, Mehra S, Tashkin DP. Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180:948–955. doi: 10.1164/rccm.200906-0876OC.
    1. Celli B, Decramer M, Leimer I, Vogel U, Kesten S, Tashkin DP. Cardiovascular safety of tiotropium in patients with COPD. Chest. 2010;137:20–30. doi: 10.1378/chest.09-0011.
    1. Anzueto A, Wise R, Pledger G, Calverley P, Dusser D, Cotton D, Devins T, Disse B, Joseph E, Kattenbeck S, et al. The tiotropium safety and performance in respimat (tiospir) trial: Bronchodilator efficacy in a spirometry substudy. Chest. 2013;144:1027A. doi: 10.1378/chest.1783312.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner