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Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study.

ABSTRACT: We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, open-label tiotropium 18 μg or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149 versus its monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety. Trough FEV1 at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health status versus placebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated. Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist combinations for the treatment of COPD.

SUBMITTER: Bateman ED

PROVIDER: S-EPMC3844137 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study.

Bateman Eric D ED Ferguson Gary T GT Barnes Neil N Gallagher Nicola N Green Yulia Y Henley Michelle M Banerji Donald D

The European respiratory journal 20130530 6

We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 μg/glycopyrronium 50 μg), indacaterol 150 μg, glycopyrronium 50 μg, op ...[more]

PMID: 23722616

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Project description:Background:Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions. Materials and methods:A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting β2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]). Results:Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD. Conclusion:These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.

Project description:IntroductionThe fixed-dose, long-acting bronchodilator combination of umeclidinium/vilanterol (UMEC/VI) has not previously been compared with a combination of a long-acting muscarinic antagonist and long-acting β2-agonist in patients with chronic obstructive pulmonary disease (COPD).MethodsThis 12-week, randomized, blinded, triple-dummy, parallel-group, non-inferiority study compared once-daily UMEC/VI 62.5/25 mcg with once-daily tiotropium (TIO) 18 mcg + indacaterol (IND) 150 mcg in patients with moderate-to-very-severe COPD. The primary endpoint was the trough forced expiratory volume in 1 s (FEV1) on day 85 (predefined non-inferiority margin -50 mL), and the secondary endpoint was the 0- to 6-h weighted mean (WM) FEV1 on day 84. Other efficacy endpoints [including rescue medication use, the Transition Dyspnea Index (TDI) focal score, and the St. George's Respiratory Questionnaire (SGRQ) score] and safety endpoints [adverse events (AEs), vital signs, and COPD exacerbations] were also assessed.ResultsTrough FEV1 improvements were comparable between treatment groups [least squares (LS) mean changes from baseline to day 85: UMEC/VI 172 mL; TIO + IND 171 mL; treatment difference 1 mL; 95 % confidence interval (CI) -29 to 30 mL], demonstrating non-inferiority between UMEC/VI and TIO + IND. The treatments produced similar improvements in the trough FEV1 at other study visits and the 0- to 6-h WM FEV1 (LS mean changes at day 84: UMEC/VI 235 mL; TIO + IND 258 mL; treatment difference -23 mL; 95 % CI -54 to 8 mL). The results for patient-reported measures (rescue medication use, TDI focal score, and SGRQ score) were comparable; both treatments produced clinically meaningful improvements in TDI and SGRQ scores. The incidence of AEs and COPD exacerbations, and changes in vital signs were similar for the two treatments.ConclusionUMEC/VI and TIO + IND, given once daily, provided similar improvements in lung function and patient-reported outcomes over 12 weeks in patients with COPD, with comparable tolerability and safety profiles.Trial numbersClinicalTrials.gov study ID NCT02257385; GSK study no. 116961.

Project description:BackgroundThe 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.MethodsIn 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. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.ResultsOverall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).ConclusionThese findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.

Project description:ObjectiveTo evaluate and compare the impact of single- versus dual-antiplatelet (SAPT vs DAPT) therapy on coagulation profiles and postoperative outcomes in patients with peripheral arterial disease (PAD).MethodsPatients with PAD undergoing lower extremity revascularization from December 2020 to August 2023 were prospectively enrolled in this cohort study and followed for one year to record the incidence of thrombotic events (TEs). These events include arterial graft/stent occlusion or stenosis, as identified through Doppler ultrasonography or angiography. Patients were categorized by type of intervention (open vs. endovascular) and further stratified by thromboprophylaxis regimen (SAPT vs DAPT). Descriptive statistics were conducted to characterize each group. Differences in continuous variables were analyzed using Student's t-test, while categorical variables were evaluated using Fisher's exact test. Kaplan-Meier survival curves and cox proportional hazard assessed the thrombosis probability between groups.ResultsA total of 157 patients were analyzed, of which 56 were open and 101 were endovascular. In the endovascular group, the majority of patients were on DAPT (61.4%), whereas in the open procedure, most individuals were on SAPT (78.6%). DAPT recipients exhibited a lower prothrombotic profile than SAPT recipients in either operative cohort (p < .05). However, the incidence of index TEs was similar between medication groups within each cohort over the one-year follow-up period. DAPT was associated with a decreased incidence of recurrent TEs in the open intervention group (p < .001), indicating its potential for reducing subsequent thrombotic complications following an index TE. Additionally, there was no significant difference in thrombosis probability between endovascular and open procedures (p = .73), nor between DAPT and SAPT groups across both procedure modalities (p = .98).ConclusionWhile DAPT demonstrated lower prothrombotic thromboelastography with platelet mapping profiles compared to SAPT, this did not translate into differences in index TEs across surgical modalities.

Project description:ObjectivesAntiplatelet therapy following peripheral arterial endovascular intervention lacks high quality evidence to guide practice. The aim of this study was to assess the effect of three months of dual antiplatelet therapy on amputation-free survival following peripheral arterial endovascular intervention in patients with chronic limb threatening ischemia.MethodsA retrospective review of symptomatic patients undergoing primary peripheral arterial endovascular intervention over a seven-year period was performed. The primary outcome measure was amputation-free survival. A sample size calculation based on previous cohort studies suggested that 629 limbs would be required to show a difference between single and dual therapy. Kaplan-Meier estimates and multivariate logistic regression analysis of recorded baseline characteristics was performed to determine predictors of amputation-free survival. Dual antiplatelet therapy was routinely given for 3 months.Results754 limbs were treated with primary angioplasty and/or stenting over a 7-year period, 508 of these for chronic limb threatening ischemia. There was no difference in unadjusted amputation-free survival between patients with chronic limb threatening ischaemia taking single vs. dual antiplatelet therapy (69% vs. 74% respectively Log rank Chi2 = 0.1, p = .72). After adjusting for confounders, at 1 year there was also no significant difference in amputation-free survival between patients taking single vs. dual antiplatelet therapy [OR 0.8, 95% CI 0.5-1.2, p = .3]. There was no difference in rates of major bleeding between single and dual antiplatelet therapy.ConclusionsThere was no clear evidence of reduced amputation-free survival in patients with chronic limb threatening ischemia undergoing peripheral arterial endovascular intervention being treated with dual antiplatelet therapy for 3 months. This is at odds with other retrospective case series and highlights the limitations in basing clinical practice on such data. There is a need for an adequately powered, independent randomised trial to definitively answer the question.

Dataset Information

Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study.

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Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study.

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