Tiotropium in combination with placebo, salmeterol, or fluticasone- salmeterol for treatment of chronic obstructive pulmonary disease: A randomized trial
ABSTRACT Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied.
To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone.
Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006.
27 academic and community medical centers in Canada.
449 patients with moderate or severe COPD.
1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol.
The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics.
The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo.
More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists.
Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.
- SourceAvailable from: Mohsen Sadatsafavi
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- "The case study is based on the OPTIMAL trial, a multicenter study evaluating the benefits of combination pharmacological therapy in preventing respiratory exacerbations in patients with chornic, obstructive pulmonary disease (COPD) [32,33]. Pharmacological treatment of COPD, typically with inhaled medications, is often required to keep the symptoms under control and reduce the risk of exacerbations. "
ABSTRACT: BACKGROUND: Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. METHODS: We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. RESULTS: In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. CONCLUSIONS: The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes.Trials 06/2014; DOI:10.1186/1745-6215-15-201 · 1.73 Impact Factor
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- "Improving health status is an important goal in the treatment of COPD patients . Inhaled glucocorticoids, long-acting beta2-agonists, and long-acting anticholinergics have all been shown to reduce exacerbation frequency in COPD, but despite these therapies, the average frequency of acute exacerbations still remains approximately 1.4 each year . An addition to the usual therapy is long-term macrolide use, of which the mechanism of action is attributed to the immunomodulatory effects as well as to diverse actions that suppress microbial virulence factors beyond their antibacterial effects [12-14]. "
ABSTRACT: Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough. In this randomised controlled trial 84 patients met the eligibility criteria: age of >=40 years, COPD GOLD stage >=2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored. Mean age of participants was 68 +/- 10 years and mean FEV1 was 1.36 +/- 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 +/- 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found. Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.Trial registration: ClinicalTrials.gov NCT01071161.Respiratory research 11/2013; 14(1):125. DOI:10.1186/1465-9921-14-125 · 3.09 Impact Factor
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- "These findings highlighted the urgent need for improvements in COPD diagnosis and management in general practice. Most diagnosed patients are treated with bronchodilators such as long-acting β2 agonists (LABAs) or long-acting antimuscarinics (LAMAs) as monotherapy, and remain symptomatic.13 It has now been recognized that monotherapy may not enable many patients to achieve the goals of pharmacologic therapy for COPD, namely to control symptoms, improve health status, and reduce the frequency of exacerbations.1 Guidelines on COPD management recommend the combined use of long-acting bronchodilators and inhaled corticosteroids (ICS) to optimize outcomes, especially exacerbations, in patients with COPD that is inadequately controlled with monotherapy.1 "
ABSTRACT: The Global initiative for chronic Obstructive Lung Disease (GOLD) Committee has proposed a chronic obstructive pulmonary disease (COPD) assessment framework focused on symptoms and on exacerbation risk. This study will evaluate a symptom and exacerbation risk-based treatment strategy based on GOLD in a real-world setting in Japan. Optimal management of COPD will be determined by assessing symptoms using the COPD Assessment Test (CAT) and by assessing the frequency of exacerbations. This study (ClinicalTrials.gov identifier: NCT01762800) is a 24-week, multicenter, randomized, double-blind, double-dummy, parallel-group study. It aims to recruit 400 patients with moderate-to-severe COPD. Patients will be randomized to receive treatment with either salmeterol/fluticasone propionate (SFC) 50/250 μg twice daily or with tiotropium bromide 18 μg once daily. Optimal management of patients will be assessed at four-weekly intervals and, if patients remain symptomatic, as measured using the CAT, or experience an exacerbation, they have the option to step up to treatment with both drugs, ie, SFC twice daily and tiotropium once daily (TRIPLE therapy). The primary endpoint of the study will be the proportion of patients who are able to remain on the randomized therapy. No data are available. This paper summarizes the methodology of the study in advance of the study starting. The results of this study will help physicians to understand whether TRIPLE therapy is more effective than either treatment strategy alone in controlling symptoms and exacerbations in patients with moderate-to-severe COPD. It will also help physicians to understand the GOLD recommendation work in Japan.International Journal of COPD 10/2013; 8:453-459. DOI:10.2147/COPD.S48298 · 3.14 Impact Factor