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

Abstract

BackgroundMany 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.MethodsIn 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).ResultsA 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.ConclusionsCVT-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.Trial registrationClinicalTrials.gov No.: NCT00818454; Registered November 16, 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0223-3) contains supplementary material, which is available to authorized users.

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…They are derivatives of the nonspecific muscarinic antagonist atropine, which acts by inhibiting the signaling of MRs to relax smooth muscles (Albertson et al, 2015;Pollock et al, 2017). They can also be used in combination with SABAs, such as albuterol or fenoterol, for increasing the efficacy over monotherapy (Bryant and Rogers, 1990;Nishi et al, 1993;Donohue et al, 2016).…”

Effectiveness of Adjunctive Mother Tinctures to Individualized Homeopathic Treatment of Chronic Obstructive Pulmonary Diseases: An Open Randomized Pragmatic Pilot Trial

“…Inclusion criteria were the cases suffering from mild to severe form of COPD (ICD J44.9) 8 : mild FEV1 !80% predicted, FEV1/FVC < 0.7, moderate FEV1 50 to 79% predicted, FEV1/ FVC < 0.7, severe FEV1 30 to 49% predicted, FEV1/FVC < 0.7, both male and female patients, age between 18 and 65 years and giving written consent to participate in the study and washout phase of conventional (e.g., bronchodilators-β 2 agonists, anticholinergics; corticosteroids, antiallergic drugs, antibiotics) or other medications for COPD, if any, of 2 weeks prior to enrolment. Usual washout phase is considered to be one week for bronchodilators 15,16 ; still, we increased it to another week to be certain of any confounding affecting the two groups. Exclusion criteria were the patients who were too sick for consultation, for example, very severe COPD, FEV1/FVC < 0.7 and FEV1 <30% predicted or <50% predicted plus chronic respiratory failure, 8 unwilling to take part and not giving consent to join the study, unable to read patient information sheet, suffering from uncontrolled systemic illness or life-threatening infections affecting quality of life, cases already undergoing homeopathic treatment for any chronic disease within last 6 months, substance abuse and/or dependence, pregnant or lactating women, patients with psychiatric diseases or unstable mental illness and selfreported immune-compromised states.…”

<p>Future perspectives of anticholinergics for the treatment of asthma in adults and children</p>

“…A subpopulation of adult patients with persistent symptomatic asthma who may benefit from treatment with macrolides has yet to be precisely defined 37. Clinical trials with azithromycin found a decrease in exacerbations in patients treated compared with those prescribed placebo, as well as an improvement in asthma-related quality of life 35.…”

“…Currently, ipratropium is recommended as an alternative reliever agent for adult patients who are unable to tolerate treatment with SABAs 46. Significant improvements in bronchodilation after 4 weeks of treatment with ipratropium bromide/albuterol combination therapy compared with albuterol alone were observed 37…”

“…A subpopulation of adult patients with persistent symptomatic asthma who may benefit from treatment with macrolides has yet to be precisely defined. 37 Clinical trials with azithromycin found a decrease in exacerbations in patients treated compared with those prescribed placebo, as well as an improvement in asthma-related quality of life. 35 Macrolides could also be considered another potential treatment to achieve disease control in patients who remain poorly controlled despite optimal inhaled treatment and who do not qualify for biologics.…”