Dataset Information

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.

ABSTRACT:

Objective

Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD.

Design

This study was a multicentre, open-label, randomised study.

Setting

Fourcentres in Kagawa prefecture, Japan.

Participant

Patients who were diagnosed to have COPD Grade 2-3 according to the Global Initiative for Chronic Obstructive Lung Disease 2015 criteria were enrolled.

Interventions

Patients were randomly assigned to receive Acli-BID or Tio-QD at a 1:1 ratio, and followed for 8 weeks. Acli-BID was administered in the morning and night, and Tio-QD was administered in the night.

Primary and secondary outcome measures

Primary outcome was forced expiratory volume in one second area under the curve (FEV₁AUC_0-3), and secondary outcomes were pulmonary function, physical activity, St George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC), the 8-item Short-Form Health Survey (SF-8) and COPD exacerbations. Adverse events were evaluated during the study.

Results

44 patients were included in this study. FEV₁AUC_0-3 at week 8 was 4.62±1.43?L·hour in Acli-BID and 4.73±1.60?L·hour in Tio-QD (mean difference (MD) -0.11?L·hour; 95% CI), -1.04 to 0.83). Significant improvement was observed in activity-related subscales of SGRQ (MD -7.78; 95%?CI -14.61 to -0.94) and SF-8 (MD 4.01; 95%?CI 0.37 to 7.65), mMRC (MD -0.66; 95%?CI -1.19 to -0.13) and rate ratio (0.52, 95%?CI 0.27 to 0.99) of exacerbations in the Acli-BID compared with the Tio-QD. Acli-BID and Tio-QD significantly improved sedentary behaviour (MD -35.20?min; 95%?CI -67.41 to -2.94 and MD -55.40?min; 95%?CI -98.15 to -12.77) within each group, but there was no significant difference between the two groups.

Conclusion

Acli-BID as with Tio-QD could be one of the therapeutic options for patients with COPD to improve pulmonary function. Also, our results suggest that intervention with bronchodilators enhanced physical activity in patients with COPD.

Trial registration number

UMIN 000020020.

SUBMITTER: Kamei T

PROVIDER: S-EPMC6661652 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.

Kamei Tadashi T Nakamura Hiroyuki H Nanki Nobuki N Minakata Yoshiaki Y Matsunaga Kazuto K Mori Yoshihiro Y

BMJ open 20190726 7

<h4>Objective</h4>Chronic obstructive pulmonary disease (COPD) is mainly treated pharmaceutically with bronchodilators. The purpose of this study was to evaluate the clinical benefits of two-times-per-day aclidinium bromide (Acli-BID) compared with once-a-day tiotropium bromide hydrate (Tio-QD) in patients with COPD.<h4>Design</h4>This study was a multicentre, open-label, randomised study.<h4>Setting</h4>Fourcentres in Kagawa prefecture, Japan.<h4>Participant</h4>Patients who were diagnosed to h ...[more]

PMID: 31350236

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Project description:IntroductionThe objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).MethodsA systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.ResultsRegarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.ConclusionBased on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.FundingAstraZeneca.

Project description:A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo. This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study.Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ?10 units) received aclidinium bromide 400 ?g twice daily (BID), tiotropium 18 ?g once daily (QD), or placebo, for 6 weeks. Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs) were assessed.In all, 277 symptomatic patients were included in this post hoc analysis. Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1) from baseline to week 6 at all time points over 24 hours versus placebo. In addition, improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 (aclidinium 157 mL, tiotropium 67 mL; P<0.001) and week 6 (aclidinium 153 mL, tiotropium 90 mL; P<0.05). Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (aclidinium 136 mL, tiotropium 68 mL; P<0.05) and week 6 (aclidinium 137 mL, tiotropium 71 mL; P<0.05). Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus tiotropium (except E-RS Chest Symptoms) and placebo over 6 weeks. Tolerability showed similar incidence of AEs in each arm.In this post hoc analysis of symptomatic patients with moderate to severe COPD, aclidinium 400 ?g BID provided additional improvements compared with tiotropium 18 ?g QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity.

Project description:IntroductionLong-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs), inhaled corticosteroids (ICS), and their combinations, are recommended for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to determine whether the safety and efficacy of aclidinium bromide differs by baseline maintenance LABA and ICS therapies.MethodsASCENT-COPD was a phase 4, multicenter, double-blind, randomized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium 400 μg or placebo twice daily, via a multidose dry-powder inhaler for up to 3 years. Outcomes included time to first major adverse cardiovascular events (MACE), all-cause mortality, change from baseline in trough forced expiratory volume in 1 s (FEV1), and COPD assessment test (CAT) total score over 3 years, and annual moderate-to-severe COPD exacerbation rate in patients receiving aclidinium or placebo with maintenance LABA monotherapy, ICS monotherapy, LABA + ICS (fixed/free), or no maintenance therapy (neither LABA nor ICS) at baseline.ResultsA total of 3589 patients were included (LABA, n = 227; ICS, n = 290; LABA + ICS, n = 2058; no maintenance, n = 1130). Aclidinium did not increase the risk of MACE or all-cause mortality versus placebo, regardless of baseline maintenance treatment. Reductions in moderate-to-severe exacerbation rates were observed with aclidinium versus placebo in all subgroups [LABA 43% (P = 0.046); ICS 25% (P = 0.202); LABA + ICS 22% (P = 0.003); no maintenance 18% (P = 0.130)]. Aclidinium improved morning trough FEV1 irrespective of baseline therapy and CAT total scores, except for LABA and ICS subgroups, versus placebo at several time points.ConclusionIn patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit.Trial registrationClinicalTrials.gov identifier NCT01966107.

Project description:Aclidinium-formoterol 400/12 µg is a long-acting muscarinic antagonist (LAMA) and a long-acting ?2-agonist in a fixed-dose combination used in the management of patients with COPD. This study aimed to assess the cost-effectiveness of aclidinium-formoterol 400/12 µg against the long-acting muscarinic antagonist aclidinium bromide 400 µg.A five-health-state Markov transition model with monthly cycles was developed using MS Excel to simulate patients with moderate-to-severe COPD and their initial lung-function improvement following treatment with aclidinium-formoterol 400/12 µg or aclidinium 400 µg. Health states were based on severity levels defined by Global Initiative for Chronic Obstructive Lung Disease 2010 criteria. The analysis was a head-to-head comparison without step-up therapy, from the NHS Scotland perspective, over a 5-year time horizon. Clinical data on initial lung-function improvement were provided by a pooled analysis of the ACLIFORM and AUGMENT trials. Management, event costs, and utilities were health state-specific. Costs and effects were discounted at an annual rate of 3.5%. The outcome of the analysis was expressed as cost (UK£) per quality-adjusted life-year (QALY) gained. The analysis included one way and probabilistic sensitivity analyses to investigate the impact of parameter uncertainty on model outputs.Aclidinium-formoterol 400/12 µg provided marginally higher costs (£41) and more QALYs (0.014), resulting in an incremental cost-effectiveness ratio of £2,976/QALY. Sensitivity analyses indicated that results were robust to key parameter variations, and the main drivers were: mean baseline forced expiratory volume in 1 second (FEV1), risk of exacerbation, FEV1 improvement from aclidinium-formoterol 400/12 µg, and lung-function decline. The probability of aclidinium-formoterol 400/12 µg being cost-effective (using a willingness-to-pay threshold of £20,000/QALY) versus aclidinium 400 µg was 79%.In Scotland, aclidinium-formoterol 400/12 µg can be considered a cost-effective treatment option compared to aclidinium 400 µg alone in patients with moderate-to-severe COPD.

Dataset Information

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.

Objective

Design

Setting

Participant

Interventions

Primary and secondary outcome measures

Results

Conclusion

Trial registration number

Publications

Clinical benefit of two-times-per-day aclidinium bromide compared with once-a-day tiotropium bromide hydrate in COPD: a multicentre, open-label, randomised study.

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