Trial Reinforces Safety of COPD Treatments
Landmark TIOSPIR™ Trial Further Reinforces Safety and Efficacy Profile of Spiriva® Respimat® in the Treatment of COPD
BRACKNELL, England, September 8, 2013 /PRNewswire/ --
One of largest chronic obstructive pulmonary disease (COPD) trials conducted to-date confirms comparable safety and efficacy profile of Spiriva ® Respimat ® 5 mcg and Spiriva ® HandiHaler ® 18 mcg
Spiriva ® Respimat ® 5mcg has a comparable mortality profile and exacerbation efficacy similar to those of Spiriva ® HandiHaler ® 18 mcg 
The TIOSPIR™ trial population was representative of typical, real-world COPD patients, including patients with the full range of COPD severities, comprehensive use of concomitant COPD medications, and patients with stable cardiac disorders [ 1]
TIOSPIR™ (Tiotropium Safety and Performance in Respimat), with over 17,000 COPD patients included, was one of the largest international COPD trials ever conducted, confirmed the comparable mortality and exacerbation efficacy profile of Spiriva® Respimat® 5 mcg and Spiriva® HandiHaler® 18 mcg. 
The results showed no difference between Spiriva® Respimat® 5 mcg and Spiriva® HandiHaler® 18 mcg in:
risk of death 
risk of first exacerbation 
on-treatment all-cause mortality 
incidents of cardiovascular adverse events 
In particular, in patients with a history of cardiac arrhythmia, there was no difference in mortality between Spiriva® Respimat® 5 mcg and Spiriva® HandiHaler® 18 mcg. 
The results from the three year trial were published in the New England Journal of Medicine on 8 September 2013. TIOSPIR™ was designed to provide evidence of the relative safety and efficacy profile of Spiriva® Respimat® 5 mcg compared with Spiriva® HandiHaler® 18 mcg.  TIOSPIR™ was specifically designed to be of an adequate size and duration, to enable analysis of all-cause mortality and risk of first COPD exacerbation in a large COPD patient population, with broad inclusion criteria, that closely reflects the real-world COPD patient population. 
Commenting on the results, Dr Richard Russell, Consultant Chest Physician, Wexham Park Hospital said "The results of this trial have been hugely anticipated and hopefully will draw a line under the debate on the safety and efficacy profile of Respimat.®
"The results provide clear evidence that Spiriva® Respimat® has an equally good mortality profile in COPD patients to Spiriva® HandiHaler®, including those with a history of cardiac disease."
The TIOSPIR™ trial demonstrated comparable results for risk of first COPD exacerbation between Spiriva® Respimat® 5 mcg and Spiriva® HandiHaler® 18 mcg. 1 In particular, the median time to the first COPD exacerbation was more than two years for both Spiriva® Respimat® 5mcg (756 days) and Spiriva® HandiHaler® 18 mcg (719 days). 
COPD exacerbations have a significant impact on patients' lives and reducing their frequency and severity are principal goals of COPD treatment.  TIOSPIR™ builds upon the established efficacy profile of Spiriva® as demonstrated in several trials, including the large-scale, POET-COPD[®]* study that was specifically powered to investigate COPD exacerbations. 
Spiriva® HandiHaler® 18 mcg demonstrated a 28% reduction in the relative risk of a COPD exacerbation leading to hospitalisation (2.1% ARR; HR=0.72; 95% CI, 0.61 to 0.85; p<0.001) compared with the long-acting beta2-agonist salmeterol, as observed in the POET-COPD®* trial 
In a separate trial Spiriva® Respimat® 5mcg demonstrated a 27% reduction in the relative risk of hospital admission due to exacerbation (1.8% ARR; HR=0.73 ; 95% CI, 0.59 -0.90; p<0.005) compared with control. 
Safety as measured by survival rates
The three year TIOSPIR™ trial also showed an comparable impact on survival - as measured by all-cause mortality for tiotropium (Spiriva® Respimat® 5 mcg vs. HandiHaler® 18 mcg).  This adds to evidence from UPLIFT[®]**, a four-year trial  in which Spiriva® HandiHaler® (18 mcg) demonstrated there was a 16% reduction in the relative risk of on-treatment mortality (the incidence rate of death was 4.79 per 100 patient years in the control group compared with 4.10 per 100 patient years in the tiotropium group HR (tiotropium/control) =0.84, 95% CI =0.73, 0.97)). 
Dr Brian Wong, Head of UK Medical and Scientific Affairs at Boehringer Ingelheim said "We are delighted with the results of this landmark TIOSPIR™ trial, which has met its primary endpoint. The study was designed to answer a specific question and we now have robust clinical evidence that Spiriva® Respimat® has similar safety and exacerbation efficacy compared with Spiriva® HandiHaler®. We hope that these results reassure healthcare professionals that they can provide a choice of device to their COPD patients."
* The POET-COPD® (The Prevention Of Exacerbations with Tiotropium in COPD) trial was a 1-year, randomised, double-blind, double-dummy, parallel-group trial with a primary endpoint of time to first exacerbation, comparing once-daily Spiriva( HandiHaler( 18 mcg with twice-daily salmeterol 50 mcg
** UPLIFT® (Understanding Potential Long-Term Impacts on Function with Tiotropium) While Spiriva ® HandiHaler ® 18 mcg did not alter the rate of decline in lung function, a co-primary study endpoint in the UPLIFT® study, it sustained greater improvements in lung function vs. control
Notes to Editors
About Spiriva ® HandiHaler ® and Spiriva ® Respimat ®
Spiriva® HandiHaler® is a breath-actuated, single-dose dry powder inhaler. 
Spiriva® Respimat® is a soft mist inhaler (SMI); an innovative delivery device which uses mechanical energy (a spring) to generate a long-lasting, slow-moving mist for inhalation. ;
Tiotropium (Spiriva®) is a long-acting muscarinic antagonist (LAMA) with a mode of action that works by opening narrowed airways by targeting a dominant reversible mechanism - cholinergic bronchoconstriction helping to keep them open for 24 hours with once-daily dosing. ;
Tiotropium is licensed for the maintenance treatment of chronic obstructive pulmonary disease (COPD) symptoms and has comprehensive clinical trial data, demonstrating extensive experience since its introduction 11 years ago and over 34 million patient years of real life experience to support its efficacy and safety profile. 
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
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For more information please visit http://www.boehringer-ingelheim.com
Date of Preparation - September 2013
(1) Wise RA, Cotton D, Dahl R et al. Tiotropium Respimat Inhaler and the Risk of Death in COPD: The TIOSPIR Trial. NEJM 2013; 369(10).
(2) National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre. Available from: http://guidance.nice.org.uk/CG101/Guidance/pdf/English . 2010.
(3) Vogelmeier C, Hederer B, Glaab T et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. N Engl J Med 2011; 364(12):1093-1103.
(4) Vogelmeier C, Hederer B, Glaab T et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. New Engl J Med: Supplemental Appendix 2011; 364(12).
(5) Bateman ED, Tashkin D, Siafakas N et al. A one-year trial of tiotropium Respimat plus usual therapy in COPD patients. Respir Med 2010; 104 (10):1460-1472. Respir Med 2010; 104(10):1460-1472.
(6) Tashkin DP, Celli B, Senn S et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008; 359(15):1543-1554.
(7) Boehringer Ingelheim. Spiriva 18 microgram inhalation powder, hard capsule. Summary of Product Characteristics. (The Electronic Medicines Compendium) http://www.medicines.org.uk/emc/medicine/10039/SPC/ . Last accessed: September 2013.
(8) Hochrainer D, Hölz H, Kreher C et al. Comparison of the aerosol velocity and spray duration of Respimat® Soft Mist™ inhaler and pressurized metered dose inhalers. J Aerosol Med 2005; 18(3):273-282.
(9) Boehringer Ingelheim. Spiriva Respimat 2.5 micrograms solution for inhalation. Summary of Product Characteristics. (The Electronic Medicines Compendium) http://www.medicines.org.uk/emc/medicine/20134/SPC/ . Last accessed: September 2013.
(10) Boehringer Ingelheim. Data on File: SPI13-02(b). 2013.
For further information, please contact:
Boehringer Ingelheim Limited
Tel: +44(0)20-7853-2227 / +44(0)7720-277117
Posted: September 2013
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