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Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

ABSTRACT: Background:Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®). Methods:This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI. Results:We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV1, 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV1 from baseline; however, the difference versus tiotropium was not significant (least squares [LS] mean difference [standard error], 17.0 [22.4] mL, P=0.4461). In a prespecified analysis of patients with FEV1 < 50% predicted, revefenacin produced an LS mean difference (95% confidence interval [CI]), 49.1 (6.3-91.9) mL in trough FEV1 and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV1 in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV1 < 50% predicted populations. Conclusions:Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV1 in patients with FEV1 < 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).

SUBMITTER: Mahler DA

PROVIDER: S-EPMC7006701 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

Mahler Donald A DA Ohar Jill A JA Barnes Chris N CN Moran Edmund J EJ Pendyala Srikanth S Crater Glenn D GD

Chronic obstructive pulmonary diseases (Miami, Fla.) 20191001 4

<h4>Background</h4>Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus ...[more]

PMID: 31647854

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Project description:BACKGROUND:Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1?s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD. METHODS:A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12?weeks. Endpoints included least squares change from baseline in trough FEV1, St. George's Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175??g and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%-<?50% and?<?30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (? 12% and???200?mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting ? agonists and/or inhaled corticosteroids, older age (>?65 and?>?75?years), and comorbidity risk factors. RESULTS:Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio?>?2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio?>?2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged >?75?years. CONCLUSIONS:Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD. TRIAL REGISTRATION:Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).

Project description:BackgroundInhaler selection is important when managing respiratory conditions; a patient's inhalation technique should be appropriate for the selected device, and patients should ideally be able to use a device successfully regardless of disease severity. The NEXThaler is a multidose dry-powder inhaler with a breath-actuated mechanism (BAM) and dose counter that activates only following inhalation, so effectively an 'inhalation counter'. We assessed inspiratory flow through the NEXThaler in two studies and examined whether inhalation triggered the BAM.MethodsThe two studies were open-label, single-arm, and single visit. One study recruited patients with asthma aged???18 years; the other recruited patients with chronic obstructive pulmonary disease (COPD) aged???40 years. All patients inhaled twice through a placebo NEXThaler. The inspiratory profile through the device was assessed for each inhalation using acoustic monitoring, with flow at and time to BAM firing, peak inspiratory flow (PIF), and total inhalation time assessed.ResultsA total of 40 patients were enrolled in the asthma study: 20 with controlled asthma and 20 with partly controlled/uncontrolled asthma. All patients were able to trigger the BAM, as evidenced by the inhalation counter activating on closing the device. Mean flow at BAM firing following first inhalation was 35.0 (range 16.3-52.3) L/min; mean PIF was 64.6 (35.0-123.9) L/min. A total of 72 patients were enrolled in the COPD study, with data analysed for 69 (mean forced expiratory volume in 1 s 48.7% predicted [17-92%]). As with the asthma study, all patients, regardless of airflow limitation, were able to trigger the BAM. Mean flow at BAM firing following first inhalation was 41.9 (26.6-57.1) L/min; mean PIF was 68.0 (31.5-125.4) L/min. Device usability was rated highly in both studies, with 5 min sufficient to train the patients, and a click heard shortly after inhalation in all cases (providing feedback on BAM firing).ConclusionsInhalation flows triggering the BAM in the NEXThaler were similar between patients with controlled and partly controlled/uncontrolled asthma, and were similar across COPD airflow limitation. All enrolled patients were able to activate the device.

Dataset Information

Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

Publications

Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

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