TY - JOUR
T1 - Efficacy and safety of ipratropium bromide/albuterol compared with albuterol in patients with moderate-to-severe asthma
T2 - A randomized controlled trial
AU - Donohue, James F.
AU - Wise, Robert
AU - Busse, William W.
AU - Garfinkel, Sandra
AU - Zubek, Valentina B.
AU - Ghafouri, Mo
AU - Manuel, Raymond C.
AU - Schlenker-Herceg, Rozsa
AU - Bleecker, Eugene R.
N1 - Funding Information:
We thank all the Investigators who participated in the study (a list of all the Investigators is provided in e-appendix 1) and Cixuang Zheng, who helped run the analysis on duration of bronchodilator response. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development. The authors received no compensation related to the development of the manuscript. This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). Writing, editorial support, and/or formatting assistance was provided by Gill Sperrin CBiol MRSB CMPP of Envision, which was contracted and compensated by BIPI for these services.
Publisher Copyright:
� 2016 Donohue et al.
PY - 2016
Y1 - 2016
N2 - 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 FEV1 area under the curve (AUC0-6) and peak (post-dose) forced expiratory volume in 1 s (FEV1) 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. FEV1 AUC0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI (p < 0.0001); peak FEV1 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 β2-agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma.
AB - 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 FEV1 area under the curve (AUC0-6) and peak (post-dose) forced expiratory volume in 1 s (FEV1) 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. FEV1 AUC0-6h response was 167 ml for ALB-HFA, 252 ml for CVT-MDI (p < 0.0001); peak FEV1 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 β2-agonist and anticholinergic treatment in moderate-to-severe, symptomatic asthma.
KW - Acute symptom relief
KW - Albuterol hydrofluoroalkaline
KW - Anticholinergic/β-agonist
KW - As-needed
KW - Bronchodilation
KW - Ipratropium bromide
KW - Ipratropium bromide/albuterol metered-dose inhaler
KW - Moderate-to-severe asthma
KW - Randomized controlled trial
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U2 - 10.1186/s12890-016-0223-3
DO - 10.1186/s12890-016-0223-3
M3 - Article
C2 - 27130202
AN - SCOPUS:85007492458
SN - 1471-2466
VL - 16
JO - BMC Pulmonary Medicine
JF - BMC Pulmonary Medicine
IS - 1
M1 - 65
ER -