Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial.

التفاصيل البيبلوغرافية
العنوان:	Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial.
المؤلفون:	Chipps BE; Capital Allergy and Respiratory Disease Center, Sacramento, CA. Electronic address: bchipps@capitalallergy.com., Israel E; Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Beasley R; Medical Research Institute of New Zealand, Wellington, New Zealand., Panettieri RA Jr; Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ., Albers FC; Avillion US Inc., Northbrook, IL., Rees R; Avillion LLP, London, UK., Dunsire L; BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Danilewicz A; Avillion LLP, London, UK., Johnsson E; BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Cappelletti C; BioPharmaceuticals R&D, AstraZeneca, Durham, NC., Papi A; Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
المصدر:	Chest [Chest] 2023 Sep; Vol. 164 (3), pp. 585-595. Date of Electronic Publication: 2023 Mar 30.
نوع المنشور:	Randomized Controlled Trial; Clinical Trial, Phase III; Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Elsevier Country of Publication: United States NLM ID: 0231335 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-3543 (Electronic) Linking ISSN: 00123692 NLM ISO Abbreviation: Chest Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2016- : New York : Elsevier Original Publication: Chicago : American College of Chest Physicians
مواضيع طبية MeSH:	Budesonide* , Asthma/drug therapy , Asthma/chemically induced, Humans ; Child ; Formoterol Fumarate ; Metered Dose Inhalers ; Administration, Inhalation ; Albuterol ; Double-Blind Method ; Bronchodilator Agents ; Treatment Outcome
مستخلص:	Background: In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy. Research Question: Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma? Study Design and Methods: This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV 1 area under the curve from 0 to 6 h (FEV 1 AUC 0-6h ) over 12 weeks (assessing albuterol effect) and trough FEV 1 at week 12 (assessing budesonide effect). Results: Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV 1 AUC 0-6h over 12 weeks was greater with albuterol-budesonide 180/160 μg vs budesonide 160 μg (least-squares mean [LSM] difference, 80.7 [95% CI, 28.4-132.9] mL; P = .003). Change in trough FEV 1 at week 12 was greater with albuterol-budesonide 180/160 and 180/80 μg vs albuterol 180 μg (LSM difference, 132.8 [95% CI, 63.6-201.9] mL and 120.8 [95% CI, 51.5-190.1] mL, respectively; both P < .001). Day 1 time to onset and duration of bronchodilation with albuterol-budesonide were similar to those with albuterol. The albuterol-budesonide adverse event profile was similar to that of the monocomponents. Interpretation: Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT03847896; URL: www. Clinicaltrials: gov. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة:	Keywords: albuterol-ICS; albuterol-budesonide; asthma; bronchodilators; inflammation; inhaled corticosteroid; rescue therapy; short-acting β(2)-agonist
سلسلة جزيئية:	ClinicalTrials.gov NCT03847896
المشرفين على المادة:	51333-22-3 (Budesonide) W34SHF8J2K (Formoterol Fumarate) QF8SVZ843E (Albuterol) 0 (Bronchodilator Agents)
تواريخ الأحداث:	Date Created: 20230401 Date Completed: 20230911 Latest Revision: 20230927
رمز التحديث:	20231215
DOI:	10.1016/j.chest.2023.03.035
PMID:	37003355
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1931-3543
DOI:	10.1016/j.chest.2023.03.035