Interpreting Evaluating Respiratory Symptoms in COPD Diary Scores in Clinical Trials: Terminology, Methods, and Recommendations.

Accurately interpreting scores on patient-reported outcome (PRO) measures is essential to understanding and communicating treatment benefit. Over the years, terminology and methods for developing recommendations for PRO score interpretation in clinical trials have evolved, leading to some confusion in the field. The phrase "minimal clinically important difference (MCID)" has been simplified to "minimal important difference (MID)" and use of responder thresholds to interpret statistically significant treatment effects has increased.

Use of the Evaluating Respiratory Symptoms™ in COPD as an Outcome Measure in Clinical Trials: A Rapid Systematic Review.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) struggle with respiratory symptoms that impair their daily activities and quality of life. Understanding a treatment's ability to relieve symptoms requires precise assessment. The Evaluating Respiratory Symptoms in COPD (E-RS:COPD) was developed to quantify respiratory symptoms in clinical trials.

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study.

Background: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 μg with twice-daily salmeterol/fluticasone (SFC) 50/500 μg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year.

Methods: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up.

Results: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.

Long-Term Maintenance Bronchodilation With Indacaterol/Glycopyrrolate Versus Indacaterol in Moderate-to-Severe COPD Patients: The FLIGHT 3 Study.

The objective of the FLIGHT3 study was to evaluate the long-term safety and efficacy of indacaterol/glycopyrrolate* (IND/GLY) versus an active comparator, IND, in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) over 52 weeks. FLIGHT3 was a multicenter, randomized, double-blind, parallel-group, 52-week study. Patients were randomized (1:1:1) to IND/GLY (27.

Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial.

Rationale: Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD).

Objectives: We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β-agonist combination versus a long-acting β-agonist/long-acting muscarinic antagonist combination for exacerbation prevention.

Methods: We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year.

Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients with COPD at a high risk of exacerbations: results from the FLAME study.

Background: The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study.

Patients And Methods: Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included.

Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD.

Background: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.

Methods: We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial.

FLIGHT1 and FLIGHT2: Efficacy and Safety of QVA149 (Indacaterol/Glycopyrrolate) versus Its Monocomponents and Placebo in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy recommends the combination of two long-acting bronchodilators of different pharmacologic classes for the management of chronic obstructive pulmonary disease (COPD) if symptoms are not adequately controlled by a single bronchodilator.

Objectives: The FLIGHT1 and FLIGHT2 studies evaluated the efficacy and safety of QVA149 (indacaterol/glycopyrrolate), a fixed-dose combination of a long-acting β2-agonist (indacaterol) and a long-acting muscarinic antagonist (glycopyrrolate), compared with its monocomponents and placebo in patients with moderate-to-severe COPD.

Methods: FLIGHT1 and FLIGHT2 were 12-week, identical, multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled studies.

LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.

Background: The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.

Methods: In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.

Effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs on urinary sodium excretion, blood pressure, and other renal function indicators in elderly subjects consuming a controlled sodium diet.

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment.

Lp(a) lipoprotein, vascular disease, and mortality in the elderly.

Background: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.

C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.

Background: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT.

Methods And Results: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study.

Self-designing two-stage trials to minimize expected costs.

In the design of clinical trials, the sample size for the trial is traditionally calculated from estimates of parameters of interest, such as the mean treatment effect, which can often be inaccurate. However, recalculation of the sample size based on an estimate of the parameter of interest that uses accumulating data from the trial can lead to inflation of the overall Type I error rate of the trial. The self-designing method of Fisher, also known as the variance-spending method, allows the use of all accumulating data in a sequential trial (including the estimated treatment effect) in determining the sample size for the next stage of the trial without inflating the Type I error rate.