Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial

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Abstract

Background

Many patients with asthma require frequent rescue medication for acute symptoms despite appropriate controller therapies. Thus, determining the most effective relief regimen is important in the management of more severe asthma. This study’s objective was to evaluate whether ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI) provides more effective acute relief of bronchospasm in moderate-to-severe asthma than albuterol hydrofluoroalkaline (ALB-HFA) alone after 4 weeks.

Methods

In this double-blind, crossover study, patients who had been diagnosed with asthma for ≥1 year were randomized to two sequences of study medication “as needed” for symptom relief (1–7 day washout before second 4-week treatment period): CVT-MDI/ALB-HFA or ALB-HFA/CVT-MDI. On days 1 and 29 of each sequence, 6-hour serial spirometry was performed after administration of the study drug. Co-primary endpoints were FEV ₁ area under the curve (AUC _0–6) and peak (post-dose) forced expiratory volume in 1 s (FEV ₁) response (change from test day baseline) after 4 weeks. The effects of “as needed” treatment with ALB-HFA/CVT-MDI were analyzed using mixed effect model repeated measures (MMRM).

Results

A total of 226 patients, ≥18 years old, with inadequately controlled, moderate-to-severe asthma were randomized. The study met both co-primary endpoints demonstrating a statistically significant treatment benefit of CVT-MDI versus ALB-HFA. FEV ₁ AUC _0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI ( p <0.0001); peak FEV ₁ response was 357 ml for ALB-HFA, 434 ml for CVT-MDI ( p <0.0001). Adverse events were comparable across groups.

Conclusions

CVT-MDI significantly improved acute bronchodilation over ALB-HFA alone after 4 weeks of “as-needed” use for symptom relief, with a similar safety profile. This suggests additive bronchodilator effects of β ₂-agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma.

Trial registration

ClinicalTrials.gov No.: NCT00818454; Registered November 16, 2009.

Electronic supplementary material

The online version of this article (doi:10.1186/s12890-016-0223-3) contains supplementary material, which is available to authorized users.

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Most cited references 32

Record: found
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Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program.

Wendy Moore, Eugene R. Bleecker, Douglas Curran-Everett … (2007)

Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P or = 12 years) was associated with lower lung function and sinopulmonary infections (P < or = .02). Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.

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Tiotropium in asthma poorly controlled with standard combination therapy.

Huib A M Kerstjens, Michael Engel, Ronald Dahl … (2012)

Some patients with asthma have frequent exacerbations and persistent airflow obstruction despite treatment with inhaled glucocorticoids and long-acting beta-agonists (LABAs). In two replicate, randomized, controlled trials involving 912 patients with asthma who were receiving inhaled glucocorticoids and LABAs, we compared the effect on lung function and exacerbations of adding tiotropium (a total dose of 5 μg) or placebo, both delivered by a soft-mist inhaler once daily for 48 weeks. All the patients were symptomatic, had a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) of 80% or less of the predicted value, and had a history of at least one severe exacerbation in the previous year. The patients had a mean baseline FEV(1) of 62% of the predicted value; the mean age was 53 years. At 24 weeks, the mean (±SE) change in the peak FEV(1) from baseline was greater with tiotropium than with placebo in the two trials: a difference of 86±34 ml in trial 1 (P=0.01) and 154±32 ml in trial 2 (P<0.001). The predose (trough) FEV(1) also improved in trials 1 and 2 with tiotropium, as compared with placebo: a difference of 88±31 ml (P=0.01) and 111±30 ml (P<0.001), respectively. The addition of tiotropium increased the time to the first severe exacerbation (282 days vs. 226 days), with an overall reduction of 21% in the risk of a severe exacerbation (hazard ratio, 0.79; P=0.03). No deaths occurred; adverse events were similar in the two groups. In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov numbers, NCT00772538 and NCT00776984.).

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Validation of a standardized version of the Asthma Quality of Life Questionnaire.

Elizabeth Juniper, A Buist, Fred M. Cox … (1999)

In the original 32-item Asthma Quality of Life Questionnaire (AQLQ), five activity questions are selected by patients themselves. However, for long-term studies and large clinical trials, generic activities may be more appropriate. For the standardized version of the AQLQ, the AQLQ(S), we formulated five generic activities (strenuous exercise, moderate exercise, work-related activities, social activities, and sleep) to replace the five patient-specific activities in the AQLQ. In a 9-week observational study, we compared the AQLQ with the AQLQ(S) and examined their measurement properties. Forty symptomatic adult asthma patients completed the AQLQ(S), the AQLQ, the Medical Outcomes Survey Short Form 36, the Asthma Control Questionnaire, and spirometry at baseline, 1, 5, and 9 weeks. Activity domain scores (mean +/- SD) were lower with the AQLQ (5.7 +/- 0.9) than with the AQLQ(S) (5.9 +/- 0.8; p = 0.0003) and correlation between the two was moderate (r = 0.77). However, for overall scores, there was minimal difference (AQLQ, 5.4 +/- 0.8; AQLQ(S), 5.5 +/- 0.8; r = 0.99). Reliability (AQLQ intraclass correlation coefficient, 0.95; AQLQ(S) intraclass correlation coefficient, 0.96) and responsiveness (AQLQ, p < 0.0001; AQLQ(S), p < 0.0001) were similar for the two instruments. Construct validity (correlation with other measures of health status and clinical asthma) was also similar for the two instruments. The AQLQ(S) has strong measurement properties and is valid for measuring health-related quality of life in asthma. The choice of instrument should depend on the task at hand.

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Author and article information

Contributors

Eugene R. Bleecker: 336-713-7520 , 336-713-7566 , ebleeck@wakehealth.edu

Journal

Journal ID (nlm-ta): BMC Pulm Med

Journal ID (iso-abbrev): BMC Pulm Med

Title: BMC Pulmonary Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2466

Publication date (Electronic): 30 April 2016

Publication date PMC-release: 30 April 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 65

Affiliations

[ ]Division of Pulmonary Diseases & Critical Care Medicine, University of North Carolina, Chapel Hill, NC USA

[ ]Pulmonary and Critical Care Division, Johns Hopkins University School of Medicine, Baltimore, MD USA

[ ]Department of Medicine, University of Wisconsin, Wisconsin, WI USA

[ ]Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT USA

[ ]Wake Forest School of Medicine, Center for Genomics and Personalized Medicine, Winston-Salem, NC 27157 USA

[ ]Previously of Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT USA

Article

Publisher ID: 223

DOI: 10.1186/s12890-016-0223-3

PMC ID: 4851785

PubMed ID: 27130202

SO-VID: 4efb75e6-a2cb-4ae6-b8e7-dad4dcbee8c7

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 5 August 2015

Date accepted : 14 April 2016

Funding

Funded by: Boehringer Ingelheim Pharmaceuticals, Inc.

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: randomized controlled trial,moderate-to-severe asthma,ipratropium bromide,albuterol hydrofluoroalkaline,ipratropium bromide/albuterol metered-dose inhaler,anticholinergic/β2-agonist,bronchodilation,as-needed,acute symptom relief

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: randomized controlled trial, moderate-to-severe asthma, ipratropium bromide, albuterol hydrofluoroalkaline, ipratropium bromide/albuterol metered-dose inhaler, anticholinergic/β2-agonist, bronchodilation, as-needed, acute symptom relief

Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma: a randomized controlled trial

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Abstract

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Conclusions

Trial registration

Electronic supplementary material

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Inflamed lung in vitro co-culture models

Most cited references 32

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program.

Tiotropium in asthma poorly controlled with standard combination therapy.

Validation of a standardized version of the Asthma Quality of Life Questionnaire.

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