A randomized study of tiotropium Respimat® Soft MistTM Inhaler vs. ipratropium pMDI in COPD

Abstract

The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.

Testing Two Different Doses of Tiotropium Respimat® in Cystic Fibrosis: Phase 2 Randomized Trial Results

“…However, the long-term effects of maintenance therapy with ipratropium bromide have not been studied in CF. Tiotropium bromide (hereafter referred to as tiotropium), a long-acting anticholinergic compound delivered as an aqueous solution using the Respimat Soft Mist Inhaler, has consistently shown superior efficacy to ipratropium [7], and is well tolerated in the treatment of chronic obstructive pulmonary disease (COPD); these findings are consistent with those observed with the tiotropium 18 µg HandiHaler [8]. Tiotropium Respimat therefore has the potential to alleviate airflow obstruction in people with CF.…”

Tiotropium mist inhaler for COPD increases risk of mortality compared with placebo

“…However, these two devices have very different safety profiles as has been shown in previously published trials1 2 and this current systematic review. The comparison with placebo is clinically important and relevant as previously published large-scale trials have compared Spiriva using inappropriate controls as in the POET-COPD trial, published earlier this year, that used salmeterol as the control 3.…”

Sequential comparison of tiotropium to high-dose ipratropium in patients with chronic obstructive pulmonary disease in a practice setting

“…However, in clinical practice use of a higher dose of ipratropium to achieve a dose of 160 µg at each dosing time would be problematic because of the large number of 6 with tiotropium compared to placebo, ipratropium and long-acting β 2 -agonists. [9][10][11][12][13] Tiotropium was shown to improve FEV 1 regardless of the presence or absence of short-term improvement in FEV 1 .…”