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The frequency of COPD exacerbations during treatment with a triple inhaler — delivering a long-acting beta-agonist (LABA), a long-acting muscarinic antagonist (LAMA), and an inhaled glucocorticoid — was compared with that with a LABA–LAMA or LABA–inhaled glucocorticoid.

In an open-label, randomized trial conducted in 75 general practices, once-daily treatment for chronic obstructive pulmonary disease with inhaled fluticasone furoate–vilanterol was associated with a lower rate of moderate or severe exacerbations than usual care. Guidelines on the management of chronic obstructive pulmonary disease (COPD) are based on numerous randomized, controlled trials of efficacy, which are usually generated for registration purposes. 1 However, these trials have included patients who were selected with the use of strict criteria and were closely monitored, and therefore the results have limited relevance to everyday clinical practice. 2 To counter this, it has been proposed that integrated comparative effectiveness trials involve more representative patients and be conducted in much less restricted environments. 3 – 5 The Salford Lung Study was designed to evaluate the effectiveness and safety of the once-daily inhaled combination of fluticasone . . .

•Persistent asthma may be better controlled by adding a long-acting muscarinic antagonist to inhaled corticosteroid + long-acting β agonist combination.•Metered dose inhaler of a novel long-acting muscarinic antagonist + long-acting β agonist + inhaled corticosteroid combination is tested.•Vilanterol 25 µg, glycopyrronium 50 µg, and fluticasone furoate 200 µg were tested.•Indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg were used as reference.•Test drugs were found to be noninferior to reference drugs.•Test drugs were well tolerated. This study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of vilanterol 12.5 µg, glycopyrronium 25 µg, and fluticasone furoate 100 µg (VIL-GLY-FF)–metered dose inhaler (MDI) (developed by M/s. Zydus Healthcare Limited) in comparison with the approved FDC of indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg (IND-GLY-MF)–dry powder inhaler (DPI) in patients with persistent asthma. Patients were randomized (1:1) in either the test (VIL-GLY-FF-MDI) or reference (IND-GLY-MF-DPI) group. Fixed-dose combinations were administered once daily for 12 weeks; for VIL-GLY-FF-MDI, patients were instructed to administer TWO actuations at 1 time in a day, doubling the final doses delivered of its components. For IND-GLY-MF-DPI, (Zydus Healthcare Limited, Ahmedabad) patients inhaled 1 capsule via the Respihaler device once daily. The primary objective was to compare the between-group difference in the change in trough forced expiratory volume in 1 second (FEV1) at week 12 from baseline. A total of 256 patients were enrolled. The change in least square mean (SE) in trough FEV1 at week 12 from baseline was 287.15 (18.00) mL and 284.94 (17.93) mL for the test and reference groups, respectively. For a predefined −150 mL noninferiority margin, 2-sided 95% CIs (−47.83 to 52.26 mL) for the difference in the mean change in trough FEV1 (2.21 mL) between the 2 groups reported the noninferiority of VIL-GLY-FF-MDI to IND-GLY-MF-DPI. The test FDC was well tolerated. Efficacy and safety of VIL-GLY-FF-MDI were found to be similar to those of IND-GLY-MF-DPI in Indian patients with persistent asthma. Clinical Trial Registry India identifier: CTRI/2024/01/061230.

Background Prospective evidence is lacking regarding incremental benefits of long-acting dual- versus mono-bronchodilation in improving symptoms and preventing short-term disease worsening/treatment failure in low exacerbation risk patients with chronic obstructive pulmonary disease (COPD) not receiving inhaled corticosteroids. Methods The 24-week, double-blind, double-dummy, parallel-group Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised patients at low exacerbation risk not receiving inhaled corticosteroids, to umeclidinium/vilanterol 62.5/25 μg once-daily, umeclidinium 62.5 μg once-daily or salmeterol 50 μg twice-daily. The primary endpoint was trough forced expiratory volume in 1 s (FEV 1 ) at Week 24. The study was also powered for the secondary endpoint of Transition Dyspnoea Index at Week 24. Other efficacy assessments included spirometry, symptoms, heath status and short-term disease worsening measured by the composite endpoint of clinically important deterioration using three definitions. Results Change from baseline in trough FEV 1 at Week 24 was 66 mL (95% confidence interval [CI]: 43, 89) and 141 mL (95% CI: 118, 164) greater with umeclidinium/vilanterol versus umeclidinium and salmeterol, respectively (both p  < 0.001). Umeclidinium/vilanterol demonstrated consistent improvements in Transition Dyspnoea Index versus both monotherapies at Week 24 (vs umeclidinium: 0.37 [95% CI: 0.06, 0.68], p  = 0.018; vs salmeterol: 0.45 [95% CI: 0.15, 0.76], p  = 0.004) and all other symptom measures at all time points. Regardless of the clinically important deterioration definition considered, umeclidinium/vilanterol significantly reduced the risk of a first clinically important deterioration compared with umeclidinium (by 16–25% [ p  < 0.01]) and salmeterol (by 26–41% [ p  < 0.001]). Safety profiles were similar between treatments. Conclusions Umeclidinium/vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimise therapy in this patient group.

Abstract Rationale Patients with chronic obstructive pulmonary disease develop increased cardiovascular morbidity with structural alterations. Objectives To investigate through a double-blind, placebo-controlled, crossover study the effect of lung deflation on cardiovascular structure and function using cardiac magnetic resonance. Methods Forty-five hyperinflated patients with chronic obstructive pulmonary disease were randomized (1:1) to 7 (maximum 14) days inhaled corticosteroid/long-acting β2-agonist fluticasone furoate/vilanterol 100/25 μg or placebo (7-day minimum washout). Primary outcome was change from baseline in right ventricular end-diastolic volume index versus placebo. Measurements and Main Results There was a 5.8 ml/m2 (95% confidence interval, 2.74–8.91; P < 0.001) increase in change from baseline right ventricular end-diastolic volume index and a 429 ml (P < 0.001) reduction in residual volume with fluticasone furoate/vilanterol versus placebo. Left ventricular end-diastolic and left atrial end-systolic volumes increased by 3.63 ml/m2 (P = 0.002) and 2.33 ml/m2 (P = 0.002). In post hoc analysis, right ventricular stroke volume increased by 4.87 ml/m2 (P = 0.003); right ventricular ejection fraction was unchanged. Left ventricular adaptation was similar; left atrial ejection fraction improved by +3.17% (P < 0.001). Intrinsic myocardial function was unchanged. Pulmonary artery pulsatility increased in two of three locations (main +2.9%, P = 0.001; left +2.67%, P = 0.030). Fluticasone furoate/vilanterol safety profile was similar to placebo. Conclusions Pharmacologic treatment of chronic obstructive pulmonary disease has consistent beneficial and plausible effects on cardiac function and pulmonary vasculature that may contribute to favorable effects of inhaled therapies. Future studies should investigate the effect of prolonged lung deflation on intrinsic myocardial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01691885).

Background Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma. Objective To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma. Methods This randomised double-blind comparative study of variable duration (≥24–78 weeks) was designed to finish after 330 events (each patient's first on-treatment severe asthma exacerbation). 2019 patients with asthma aged ≥12 years with ≥1 recorded exacerbation within 1 year were randomised and received FF/VI 100/25 μg or FF 100 μg, administered once daily in the evening. The primary endpoint was time to first severe exacerbation; secondary endpoints were rate of severe asthma exacerbations per patient per year and change in trough evening forced expiratory volume in 1 s (FEV1) from baseline. Results Compared with FF, FF/VI delayed the time to first severe exacerbation (HR 0.795, 95% CI 0.642 to 0.985) and reduced the annualised rate of severe exacerbations (rate reduction 25%, 95% CI 5% to 40%). Significantly greater improvements in trough FEV1 (p<0.001) were observed with FF/VI than with FF at weeks 12, 36, 52 and at endpoint. Both treatments were well tolerated with similar rates of treatment-related adverse events and on-treatment serious adverse events. Conclusions Once-daily FF/VI reduced the risk of severe asthma exacerbations and improved lung function compared with FF alone, with good tolerability and safety profile in adolescents and adults with asthma currently receiving ICS. ClinicalTrials.gov No NCT01086384

The INTREPID trial showed that once-daily single-inhaler triple therapy (SITT) using fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) offers clinical benefits versus non-ELLIPTA multiple-inhaler triple therapy (MITT) for the management of chronic obstructive pulmonary disease (COPD) in real-world clinical practice. This analysis evaluated the cost-effectiveness of SITT with FF/UMEC/VI versus non-ELLIPTA MITT for treating symptomatic COPD from a German healthcare perspective. Data from the INTREPID trial, including baseline characteristics, treatment effects (forced expiratory volume in 1 second and St. George's Respiratory Questionnaire score [derived from exploratory COPD assessment test score mapping]), and discontinuation rates, along with German healthcare resource and drug costs (2023 Euros), were used to populate the GALAXY COPD model. The analysis was conducted over a lifetime horizon, with outcomes including life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-utility ratios. The robustness of the analysis was assessed using scenario, one-way sensitivity, and probabilistic analyses. Improved lifetime outcomes were predicted for FF/UMEC/VI versus non-ELLIPTA MITT, providing additional LYs of 0.174 (95% range: 0.065, 0.322) and QALYs of 0.261 (0.186, 0.346) per patient, together with cost savings of €2,850 (€3,517, €2,220). Additionally, patients receiving FF/UMEC/VI were predicted to experience a reduction in exacerbations (-0.063), highlighting its dominance as the preferred treatment option. These findings remained consistent across one-way sensitivity, scenario, and probabilistic analyses, highlighting the robustness of FF/UMEC/VI as a cost-effective solution for COPD management in Germany. FF/UMEC/VI offers clinical benefits and cost savings compared with non-ELLIPTA MITT, suggesting that it may reduce the burden of COPD in Germany and warranting consideration as a preferred treatment option by physicians.

This study aimed to report the effects of policosanol (20 mg/day) on blood pressure values in Cuban patients with grade I hypertension. A double‐blind multicenter trial randomized 400 eligible patients divided into two strata of patients with either prehypertension or grade I hypertension (200 patients each) treated with either placebo or policosanol 20 mg/day (100 patients/group/stratum) for 12 weeks. Having published the results of pre‐hypertensive patients, here we report the grade I hypertension stratum (SBP 140–159 mmHg, DBP 90–99 mmHg) results. The primary outcome targeted whether policosanol could achieve significant systolic blood pressure (SBP) reductions ≥10 mmHg versus baseline and significantly different from placebo. Changes in diastolic blood pressure (DBP) and lipid profile variables were secondary outcomes. Safety indicators and adverse events were assessed. Statistical analyses were conducted by Intention to Treat. Both groups were similar at randomization. At study completion, policosanol significantly lowered (p < 0.001) SBP, the primary outcome, by more than 10 mmHg related to baseline and placebo, while also significantly decreasing (p < 0.001) DBP values versus baseline and placebo. Also, more (p < 0.001) policosanol patients reached SBP reductions ≥10 mmHg and DBP reductions ≥5 mmHg versus baseline (74% and 91%, respectively) than placebo patients (12% and 15%, respectively). Policosanol significantly lowered low‐density lipoprotein‐cholesterol (LDL‐C) and total cholesterol, while increasing high‐density lipoprotein‐cholesterol (HDL‐C). It is concluded that oral administration of policosanol 20 mg/day for twelve weeks significantly lowered SBP and DBP in Cuban patients with grade I hypertension, and improved lipid profile variables, being safe and well tolerated. Trial registration: Cuban Public Registry of Clinical Trials identifier: RPCEC00000377; IRB approval number: IRB‐120721.

Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date. To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF) in patients with COPD with an exacerbation history. Two replicate, 1-year, double-blind clinical trials enrolled subjects with COPD with moderate to very severe airflow limitation and at least one exacerbation within the prior year. Subjects were randomized 1:1:1:1 to receive inhaled once-daily vilanterol (VI) 25 μg or VI 25 μg combined with 50, 100, or 200 μg FF. Subjects were required to have a chest radiograph at screening and within 48 hours of any suspected pneumonia or exacerbation. Among 3,255 randomized subjects, 205 pneumonia events occurred in 181 subjects. Chest imaging was available for 195 (95%) of these events. Chest radiographs were also obtained for 1,793 (70%) of the 2,545 moderate and severe exacerbations. For VI alone and the combination with 50, 100, or 200 μg FF, reported pneumonia incidence was 3, 6, 6, and 7%, respectively. However, for events with compatible parenchymal infiltrates, the respective incidences were 2, 4, 4, and 5%. Factors associated with at least a twofold increase in the risk of pneumonia with FF/VI treatment were being a current smoker, having prior pneumonia, body mass index <25 kg/m(2), and severe airflow limitation. Radiographically confirmed pneumonia risk is increased with inhaled FF/VI, although at less than investigator-defined rates. Modifiable pneumonia risk factors should be considered when attempting to optimize COPD management. Clinical trial registered with www.clinicaltrials.gov (NCT01009463 [HZC102871]; NCT01017952 [HZC102970]).

Background Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. Methods Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM ® . Results The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/ F ) with FF CL/ F 35% lower in patients of Japanese heritage across all treatments and FF CL/ F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/ F and weight on apparent volume of distribution (V2/ F ) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/ F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/ F and approximately an 8% increase in UMEC V2/ F . For a subject with COPD who smoked, UMEC CL/ F was 28% higher. For VI, weight on CL/ F and smoking status on V2/ F with an approximately 4% increase in VI CL/ F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/ F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. Conclusions All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI + UMEC, or the dual combinations FF/VI and/or UMEC/VI.