Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
ERJ Open Res ; 4(1)2018 Jan.
Article in English | MEDLINE | ID: mdl-29322050

ABSTRACT

This multicentre, randomised, double-blind, placebo-controlled, two-period crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) using the endurance shuttle walk test (ESWT). Patients were randomised 1:1 to one of two treatment sequences: 1) UMEC/VI 62.5/25 µg followed by placebo or 2) placebo followed by UMEC/VI 62.5/25 µg. Each treatment was taken once daily for 12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET) at week 12. Secondary end-points included trough forced expiratory volume in 1 s (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12. COPD Assessment Test (CAT) score at week 12 was also assessed. UMEC/VI treatment did not result in a statistically significant improvement in EET change from baseline at week 12 versus placebo (p=0.790). However, improvements were observed in trough FEV1 (206 mL, 95% CI 167-246), 3-h post-dose FRC (-346 mL, 95% CI -487 to -204) and CAT score (-1.07 units, 95% CI -2.09 to -0.05) versus placebo at week 12. UMEC/VI did not result in improvements in EET at week 12 versus placebo, despite improvements in measures of lung function, hyperinflation and health status.

2.
Article in English | MEDLINE | ID: mdl-28280319

ABSTRACT

INTRODUCTION: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO). METHODS: In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs). RESULTS: Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2-0.0]; P≤0.05). More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01). Improvements in SGRQ and CAT scores were similar between treatments. The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%). CONCLUSION: UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.


Subject(s)
Benzyl Alcohols/administration & dosage , Bronchodilator Agents/administration & dosage , Chlorobenzenes/administration & dosage , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinuclidines/administration & dosage , Tiotropium Bromide/administration & dosage , Aged , Argentina , Benzyl Alcohols/adverse effects , Bronchodilator Agents/adverse effects , Chlorobenzenes/adverse effects , Drug Substitution , Europe , Female , Forced Expiratory Volume , Humans , Intention to Treat Analysis , Least-Squares Analysis , Logistic Models , Lung/physiopathology , Male , Middle Aged , Muscarinic Antagonists/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Quinuclidines/adverse effects , Recovery of Function , South Africa , Surveys and Questionnaires , Time Factors , Tiotropium Bromide/adverse effects , Treatment Outcome , United States , Vital Capacity
3.
Pulm Pharmacol Ther ; 31: 85-91, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25197005

ABSTRACT

BACKGROUND: The bronchodilator response to short-acting ß2-agonist and short-acting muscarinic antagonist monotherapies varies on a day-to-day basis within individual patients. The objective of this study was to compare daily variation in bronchodilator response to the combined use of albuterol and ipratropium with monotherapies in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a 4-week, randomized, open-label, two-period crossover study in patients with COPD. Patients were randomized 1:1 to receive albuterol via metered dose inhaler followed by ipratropium or vice versa during treatment Period 1 (10-14 days). The order of treatments was then reversed during treatment Period 2 (10-14 days). Pre-defined efficacy endpoints were: forced expiratory volume in 1 s (FEV1), derived FEV1, inspiratory capacity (IC) and daily variability of FEV1 and IC as measured by coefficient of variation (CV). RESULTS: Albuterol and ipratropium improved FEV1 when administered as the first bronchodilator, compared with pre-dose values (0.269 and 0.243 L, respectively). Administration of the second bronchodilator provided further improvements in lung function, but to a lesser magnitude than the first bronchodilator (0.094 L for both treatments). A statistically significant reduction in daily variability in FEV1 was observed for dual bronchodilator therapy compared with monotherapy (difference in CV = 0.007; p = 0.019) and pre-dose values (no treatment; difference in CV = 0.022; p < 0.001). CONCLUSIONS: The free combination of albuterol and ipratropium resulted in greater improvements and lower day-to-day variability in FEV1 compared with either monotherapy or no bronchodilator therapy. The reduced daily variability may be an important therapeutic advantage of using different classes of bronchodilators in COPD. TRIAL REGISTRATION: NCT01691482.


Subject(s)
Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Ipratropium/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Aged , Albuterol/administration & dosage , Bronchodilator Agents/administration & dosage , Cross-Over Studies , Drug Administration Schedule , Drug Therapy, Combination , Female , Forced Expiratory Volume , Humans , Ipratropium/administration & dosage , Male , Middle Aged , Respiratory Function Tests
4.
Chest ; 145(5): 981-991, 2014 May.
Article in English | MEDLINE | ID: mdl-24385182

ABSTRACT

BACKGROUND: Combination long-acting bronchodilator therapy may be more effective than long-acting bronchodilator monotherapy in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To compare the efficacy and safety of once-daily umeclidinium/vilanterol (UMEC/VI) 125/25 mcg with placebo and UMEC or VI monotherapy in COPD. METHODS: This was a double-blind, placebo-controlled, parallel-group study. A total of 1493 patients were randomized (3:3:3:2) to 24 weeks of treatment with UMEC/VI 125/25 mcg, UMEC 125 mcg, VI 25 mcg, or placebo once-daily via dry powder inhaler. RESULTS: Primary efficacy endpoint was trough forced expiratory volume in one second (FEV1) on Day 169 (23-24 h post-dose). Additional lung-function, symptomatic and health-related quality of life endpoints were also assessed. Safety evaluations included: adverse events, vital signs, electrocardiography and clinical laboratory measurements. All active treatments significantly improved trough FEV1 vs placebo (0.124-0.238 L, all p<0.001). Improvements with UMEC/VI 125/25 mcg were significantly greater than for UMEC 125 mcg or VI 25 mcg (0.079 L and 0.114 L; both p≤0.001). Improvements for UMEC/VI 125/25 mcg vs placebo were observed for the transition dyspnea index (1.0 unit; p<0.001), rescue albuterol use at Weeks 1-24 (-1.5 puffs/day) and St. George's Respiratory Questionnaire (-3.60 units, p<0.001). No safety signals were observed. CONCLUSIONS: Once-daily UMEC/VI 125/25 mcg was well tolerated and provided greater improvements in lung function, health status, and dyspnea scores compared with monotherapy components and placebo over 24 weeks. This study supports the use of UMEC/VI 125/25 mcg for the maintenance treatment of COPD. CLINICAL TRIAL REGISTRATION: protocol number: DB2113361; ClinicalTrials.gov identifier: NCT01313637.


Subject(s)
Benzyl Alcohols/administration & dosage , Bronchodilator Agents/administration & dosage , Chlorobenzenes/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , Quinuclidines/administration & dosage , Administration, Inhalation , Adult , Aged , Benzyl Alcohols/adverse effects , Benzyl Alcohols/therapeutic use , Bronchodilator Agents/adverse effects , Bronchodilator Agents/therapeutic use , Chlorobenzenes/adverse effects , Chlorobenzenes/therapeutic use , Double-Blind Method , Drug Combinations , Dry Powder Inhalers , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Quality of Life , Quinuclidines/adverse effects , Quinuclidines/therapeutic use , Treatment Outcome
5.
Chest ; 130(3): 647-56, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16963658

ABSTRACT

STUDY OBJECTIVE: To examine the effect of fluticasone propionate, 250 microg/salmeterol, 50 microg combination (FSC 250/50) twice daily on lung hyperinflation and associated measures of exercise performance in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group study. PATIENTS: Eligible patients were > or = 40 years old with a diagnosis of COPD, prealbuterol FEV(1) < 70% of predicted, FEV1/FVC ratio > or = 0.70, and functional residual capacity (FRC) > or = 120% of predicted normal. INTERVENTIONS: Patients were randomized to FSC 250/50; salmeterol, 50 microg; or placebo twice daily for 8 weeks. Predose and postdose spirometry, plethysmography, and constant-load cycle cardiopulmonary exercise test evaluations were compared. The primary comparison was FSC 250/50 with placebo. The salmeterol group was included for exploratory comparisons with FSC 250/50. RESULTS: A total of 185 patients (mean baseline FEV1 of 41% predicted) were enrolled. At rest, FSC 250/50 significantly reduced postdose FRC and increased inspiratory capacity (IC) compared with placebo (differences of - 0.35 +/- 0.12 L and 0.33 +/- 0.06 L [mean +/- SE], respectively, at week 8; p > or = 0.003) and increased exercise endurance time (difference, 132 +/- 45 s; p = 0.004). At a standardized time during exercise (isotime), FSC 250/50 increased postdose IC by 0.20 +/- 0.05 L over placebo with associated improvements in tidal volume and minute ventilation (p < 0.05 vs placebo at week 8). Improvement in exercise time was significantly correlated with the increase in IC (r = 0.45, p < 0.001) but not FEV1 (r = 0.23, p = 0.08). Predose comparisons of FSC 250/50 with salmeterol and placebo favored FSC 250/50. CONCLUSION: We conclude that FSC 250/50 decreases lung hyperinflation at rest and during exercise with an associated increase in exercise endurance time when compared with placebo.


Subject(s)
Albuterol/analogs & derivatives , Androstadienes/pharmacology , Androstadienes/therapeutic use , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Lung/drug effects , Physical Endurance/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Adrenergic beta-Agonists/adverse effects , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/therapeutic use , Aged , Albuterol/adverse effects , Albuterol/pharmacology , Albuterol/therapeutic use , Androstadienes/adverse effects , Bronchodilator Agents/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Combinations , Dyspnea/physiopathology , Female , Fluticasone-Salmeterol Drug Combination , Humans , Lung/pathology , Lung/physiopathology , Lung Volume Measurements , Male , Middle Aged , Physical Endurance/physiology , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Ventilation/drug effects , Pulmonary Ventilation/physiology , Respiratory Function Tests , Respiratory Mechanics/drug effects , Respiratory Mechanics/physiology , Salmeterol Xinafoate , Tidal Volume/drug effects , Tidal Volume/physiology , Time Factors
6.
Ann Allergy Asthma Immunol ; 92(2): 201-7; quiz 207-8, 267, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14989387

ABSTRACT

BACKGROUND: The impact of long-term inhaled corticosteroid (ICS) therapy on bone mineral density (BMD) is poorly understood. OBJECTIVE: To evaluate the impact of long-term ICS use on BMD. METHODS: Random-effects meta-analysis. Published and unpublished literature were identified by searches of MEDLINE and EMBASE databases and consultation with experts. Studies reporting BMD among adult asthma and chronic obstructive pulmonary disease (COPD) patients using ICS and non-ICS controls were identified. Studies selected for review included at least 1 year of follow-up. Two independent reviewers evaluated studies; data from those meeting specified inclusion criteria were abstracted for inclusion in the meta-analysis. RESULTS: Fourteen (5.3%) of 266 reviewed studies met specified inclusion criteria. Sufficient data were available to perform meta-analysis on 3 measures for ICS-using patients (lumbar, femoral neck, and major trochanter BMD) and 1 measure (lumbar BMD) for non-ICS-using controls. Using current National Asthma Education and Prevention Program definitions, the majority of studies (12 of 14) included patients receiving moderate to high doses of ICSs. Among ICS users, annual changes from baseline in lumbar, femoral neck, and major trochanter BMD (-0.23%, -0.17%, and +1.46%, respectively) were not statistically significant. Mean changes in lumbar BMD were also not significantly different from controls (-0.02%). Further, annual changes in lumbar BMD were not statistically significant for subgroups of patients with asthma or COPD. CONCLUSIONS: Long-term use of ICSs in patients with asthma or COPD was not associated with significant changes in BMD.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Anti-Asthmatic Agents/pharmacology , Bone Density/drug effects , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Androstadienes/administration & dosage , Androstadienes/pharmacology , Androstadienes/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Beclomethasone/administration & dosage , Beclomethasone/pharmacology , Beclomethasone/therapeutic use , Budesonide/administration & dosage , Budesonide/pharmacology , Budesonide/therapeutic use , Fluticasone , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Randomized Controlled Trials as Topic , Triamcinolone Acetonide/administration & dosage , Triamcinolone Acetonide/pharmacology , Triamcinolone Acetonide/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...