Tiotropium Group Research Articles

A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD

The aim of this pilot study was to explore the relative efficacy in terms of improvement in symptoms and lung function of combining fluticasone propionate/salmeterol combination (FSC) and tiotropium in patients with severe-to-very severe stable COPD. Ninety patients were randomized to receive 3 months of treatment in one of three treatment groups: (1) FSC 500/50 μg Diskus, 1 inhalation twice daily+placebo Handihaler 1 inhalation once-daily daily; (2) tiotropium 18 μg Handihaler, 1 inhalation once daily+placebo Diskus, 1 inhalation twice daily; (3) FSC 500/50 μg Diskus, 1 inhalation twice daily+tiotropium 18 μg Handihaler, 1 inhalation once-daily daily. Patients attended the clinic before and after 1 month, 2 months, and 3 months of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using a visual analog scale (VAS). Also the supplemental salbutamol use was measured. Eighty-one patients completed the 3-month treatment period: 26 patients receiving FSC, 26 patients receiving tiotropium, and 29 patients receiving FSC+tiotropium. Patients were withdrawn for COPD exacerbation. Improvements in trough FEV 1 with all treatments medications were observed by the first month when trough FEV 1 had improved significantly above baseline by 74 mL ( p < 0.05 ) in the tiotropium group, by 117 mL ( p < 0.05 ) in the FSC group and by 115 mL ( p < 0.05 ) in FSC+tiotropium group. At the end of the study, trough FEV 1 had improved significantly above baseline by141 mL ( p < 0.05 ) in the tiotropium group, by 140 mL ( p < 0.05 ) in the FSC group and by 186 mL ( p < 0.05 ) in FSC+tiotropium group. The difference between FSC and tiotropium appeared to decrease, that between FSC and FSC+tiotropium appeared to increase and that between tiotropium and FSC+tiotropium remained almost similar with study duration. Our results suggest that adding FSC and tiotropium may provide benefits in symptomatic patients with severe-to-very severe stable COPD.

The Effect of Tiotropium on Hyperinflation and Exercise Capacity in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, which results in the progressive development of dyspnea and exercise limitation. Objective and Methods: To compare the effect of tiotropium with placebo on forced vital capacity (FVC) in patients with moderate-to-severe COPD and lung hyperinflation, using exercise endurance, dyspnea and health-related quality of life (HRQoL) as secondary endpoints. One hundred patients were randomized to receive either tiotropium 18 µg once daily or placebo for 12 weeks. Results: Trough (predose) FVC was significantly improved with tiotropium compared to placebo on day 42 (0.27 ± 0.08 liters) and 84 (0.20 ± 0.08 liters; p < 0.05 for both). Trough inspiratory capacity (IC) was also significantly improved with tiotropium compared to placebo on day 42 (0.16 ± 0.07 liters) and 84 (0.15 ± 0.07 liters; p < 0.05 for both). Tiotropium increased the mean distance walked during the shuttle walking test by 33 ± 12 (day 42) and 36 ± 14 m (day 84) compared to placebo (p < 0.05 for both). On day 84, 59% of the patients in the tiotropium group and 35% of the patients in the placebo group had significant and clinically meaningful improvements in the St. George’s Respiratory Questionnaire total score (p < 0.05). Numerical decreases in the focal score in the Transition Dyspnea Index in patients receiving tiotropium versus placebo suggest that tiotropium also improved dyspnea during activities of daily living. Conclusion: Tiotropium 18 µg once daily reduced hyperinflation with consequent improvements in walking distance and HRQoL in patients with COPD and lung hyperinflation.

Improved daytime spirometric efficacy of tiotropium compared with salmeterol in patients with COPD

Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends long-acting bronchodilators as first-line maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). A study was conducted comparing the long-acting anticholinergic tiotropium with the long-acting beta-agonist salmeterol to confirm the significant improvements in daytime bronchodilator efficacy seen with tiotropium in previous studies. Methods Randomized, double-blind, double-dummy, parallel-group study, comparing daytime bronchodilator efficacy of tiotropium 18 mcg once daily with salmeterol 50 mcg twice daily in patients with COPD. Serial spirometry was performed over 12 h after 12 weeks of treatment. Co-primary endpoints were average (over 12 h) and peak FEV 1 at 12 weeks. Results 653 patients were randomized (328 tiotropium, 325 salmeterol): mean age 64 years; 66% male; mean baseline FEV 1 1.05 l (37.7% predicted). After 12 weeks, the average post-dose FEV 1 over 12 h was significantly higher with tiotropium compared with salmeterol (167 vs. 130 mL, respectively, p=0.03), as was peak FEV 1 (262 vs. 216 ml, respectively, p=0.01). The average FEV 1 responses from 0–6 h and 6–12 h were higher in the tiotropium group compared with salmeterol ( p<0.05). Peak and average FVC were significantly higher with tiotropium compared with salmeterol ( p<0.01). Morning pre-dose FEV 1 responses were not significantly different; however, tiotropium demonstrated a significantly higher pre-dose FVC than salmeterol ( p<0.05). Conclusion Tiotropium demonstrated significantly greater post-dose improvements in spirometric parameters compared with salmeterol. These improvements were sustained over 12 h.

A Comparison of Tiotropium 18µg, Once Daily and Ipratropium 40µg, 4 Times Daily in a Double-Blind, Double-Dummy, Efficacy and Safety Study in Adults with Chronic Obstructive Pulmonary Disease

Background : This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules ( once daily) with a ipratropium metered dose inhaler (2 puffs of q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Method : After the initial screening assessment and a two-week run-in period, patients received either tiotropium once daily or ipratropium four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second () and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. Result : In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted of 42 (12)% were analyzed. The trough response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. Conclusion : This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.

Probabilistic Markov Model to Assess the Cost-Effectiveness of Bronchodilator Therapy in COPD Patients in Different Countries

Objectives The development of a probabilistic Markov model with a time horizon of 1 year to compare the cost-effectiveness of three bronchodilators: 1) the new long-acting anticholinergic tiotropium; 2) the short-acting anticholinergic ipratropium; and 3) the long-acting beta 2-agonist salmeterol, for the treatment of patients with chronic obstructive pulmonary disease (COPD) in different countries. In this article we compare the Netherlands and Canada. Methods The Markov model was structured along disease severity states and exacerbations. Transition probabilities between disease states and exacerbation probabilities were derived from patient-level data from six randomized controlled trials assessing the efficacy and safety of tiotropium. Resource utilization during exacerbations and maintenance treatment for the Netherlands were derived from two clinical trials, whereas for Canada these data were obtained from a countrywide observational study that used similar inclusion criteria as the trials. Second-order Monte Carlo simulations were undertaken in which values were randomly drawn from distributions of these parameters. Outcomes of the model are yearly treatment costs, exacerbations, and quality-adjusted life months. Results The mean difference in the number of exacerbations was 0.17 (95% uncertainty interval: −0.02–0.37) in favor of tiotropium when compared with salmeterol and the difference between salmeterol and ipratropium was 0.12 (−0.17–0.44) in favor of salmeterol. The number of quality-adjusted life months did not substantially differ between treatment groups and varied from 8.42 (SE 0.41) in the tiotropium group to 8.17 (0.46) in the salmeterol group and 8.11 (0.50) in the ipratropium group. In the Netherlands, costs in the tiotropium group were 42 € (−484–353) lower than in the salmeterol group, whereas costs in the salmeterol group were 128€ (−795–457) lower than in the ipratropium group. In Canada, costs were consistently lower than in the Netherlands and nearly the same in all treatment groups. Differences between the two countries were primarily a result of a higher length of hospital stay in case of an exacerbation in the Netherlands. The cost-effectiveness acceptability frontier of exacerbations showed that tiotropium was associated with the maximum expected net benefit for all values of the ceiling ratio above 0€ (the Netherlands) and 10€ (Canada) in the base case analysis. Conclusions This probabilistic model-based economic evaluation demonstrates how clinical trial data can be combined and integrated with country-specific information about resource utilization and unit cost to assess the cost-effectiveness of bronchodilators in COPD patients. Quality-adjusted life months did not substantially differ between treatment groups. In terms of exacerbations, tiotropium was associated with maximum expected net benefit for plausible values of the ceiling ratio. In sensitivity analyses, this outcome was most sensitive to changes in exacerbation rates.

One-year analysis of longitudinal changes in spirometry in patients with COPD receiving tiotropium

BackgroundAirway medications have not been shown to reduce the loss of lung function in patients with COPD. We explored whether tiotropium 18μg once daily could slow the rate of decline of lung function over a 1-year period. MethodsWe performed a post-hoc analysis of data from 921 ambulatory COPD patients participating in two, 1-year, double-blind, tiotropium vs. placebo-controlled trials. Serial spirometry was obtained at baseline (before first dose of study drug), on day 8, at 6 weeks, and at 3, 6, 9 and 12 months after start of the study. ResultsBaseline demographics and lung function were comparable. Baseline FEV1 was 1.01±0.41 (SD) L (39±14% predicted). Mean decline in trough FEV1 (i.e. FEV1 23–24h after prior use of medication) between days 8 and 344 was 58ml/year in the placebo group and 12ml/year in the tiotropium group (p=0.005 vs. placebo); and between days 50 and 344 was 59ml/year in the placebo group and 19ml/year in the tiotropium group (p=0.036 vs. placebo). ConclusionsBased on a retrospective analysis of 1-year, placebo-controlled clinical trials, tiotropium was associated with a reduced rate of loss of FEV1. Longer-term trials specifically designed to study this effect are required to confirm this observation.

One-year cost-effectiveness of tiotropiumversusipratropium to treat chronic obstructive pulmonary disease

The aim of this paper is to assess the health economic consequences of substituting ipratropium with the new, once-daily bronchodilator tiotropium in patients with a diagnosis of chronic obstructive pulmonary disease (COPD). This prospective cost-effectiveness analysis was performed alongside two 1-yr randomised, double-blind clinical trials in the Netherlands and Belgium. Patients had a diagnosis of COPD and a forced expiratory volume in one second (FEV1) < or = 65% predicted normal. Patients were randomised to tiotropium (18 microg once daily) or ipratropium (2 puffs of 20 microg administered four times daily) in a ratio of 2:1. The mean number of exacerbations was reduced from 1.01 in the ipratropium group (n = 175) to 0.74 in the tiotropium group (n = 344). The percentages of patients with a relevant improvement on the St. George's Respiratory Questionnaire (SGRQ) were 34.6% and 51.2%, respectively. Compared to ipratropium, the number of hospital admissions, hospital days and unscheduled visits to healthcare providers was reduced by 46%, 42% and 36% respectively. Mean annual healthcare costs including the acquisition cost of the study drugs were 1721 Euro (SEM 160) in the tiotropium group and 1,541 Euro (SEM 163) in the ipratropium group (difference 180 Euro). Incremental cost-effectiveness ratios were 667 Euro per exacerbation avoided and 1084 Euro per patient with a relevant improvement on the SGRQ. Substituting tiotropium for ipratropium in chronic obstructive pulmonary disease patients offers improved health outcomes and is associated with increased costs of 180 Euro per patient per year.

A 6-Month, Placebo-Controlled Study Comparing Lung Function and Health Status Changes in COPD Patients Treated With Tiotropium or Salmeterol

Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD. A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 microg once daily via dry-powder inhaler, compared with salmeterol, 50 microg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ). A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV(1) (mean, 1.08 +/- 0.37 L; percent predicted, 40 +/- 12% [+/- SD]). Compared with placebo treatment, the mean predose morning FEV(1) following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV(1) (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, - 5.14 U (p < 0.05 vs placebo); salmeterol, - 3.54 U (p = 0.4 vs placebo); and placebo, - 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001). Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.

A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease

BACKGROUNDA study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).METHODS288 patients...

Clinical efficacy of tiotropium in children with asthma.

Objective:To investigate the clinical efficacy of tiotropium in children with asthma.Methods:Eighty children with newly diagnosed moderate persistent asthma were enrolled into this study. The children were randomly assigned to the fluticasone propionate aerosol group or the fluticasone propionate aerosol plus tiotropium group for 12 weeks.Results:Lung function was significantly improved in both groups at 4, 8, and 12 weeks compared with baseline (P < 0.01). Moreover, lung function was significantly improved in the tiotropium group compared with the control group (P < 0.05). However, there was no significant difference in the incidence of severe asthma between the two groups (36.3% and 26.8%, respectively; P > 0.05). Compared with the control group, the number of days and frequency of short-acting beta2-adrenoceptor agonist use was significantly reduced in the tiotropium group (P < 0.05). Awakenings during the night were also significantly decreased (P < 0.00). There were no severe adverse reactions in either of the study groups.Conclusion:Tiotropium could significantly improve lung function, reduce the use of short-acting beta2-adrenoceptor agonists, and improve sleep in children with asthma. Furthermore, few adverse reactions were reported.