Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.

Primatene MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine.

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study.

Background: Limited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment.

Objective: To explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β-agonist (SABA) usage to determine the clinical relevance of moderate events.

Methods: CAPTAIN was a phase IIIA 24- to 52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β-agonist.

How can the findings of the EMAX trial on long-acting bronchodilation in chronic obstructive pulmonary disease be applied in the primary care setting?

This review addresses outstanding questions regarding initial pharmacological management of chronic obstructive pulmonary disease (COPD). Optimizing initial treatment improves clinical outcomes in symptomatic patients, including those with low exacerbation risk. Long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual therapy improves lung function versus LAMA or LABA monotherapy, although other treatment benefits have been less consistently observed.

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial.

Background: The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).

Methods: This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18-40 years) and 1005 older adults (OAs; aged 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart.

Applying key learnings from the EMAX trial to clinical practice and future trial design in COPD.

Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a large, multicentre, multi-national, randomised, double-blind, 24-week trial. EMAX evaluated the efficacy and safety of dual bronchodilator therapy with umeclidinium bromide (UMEC)/vilanterol (VI) versus monotherapy with either UMEC or salmeterol (SAL) in symptomatic patients with chronic obstructive pulmonary disease (COPD) at low exacerbation risk who were not taking concomitant inhaled corticosteroid (ICS). EMAX generated evidence covering a wide range of patient-centred endpoints in COPD in addition to measures of lung function, clinical deterioration and safety.

Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial.

The mRNA-1273 vaccine for coronavirus disease 2019 (COVID-19) demonstrated 93.2% efficacy in reduction of symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the blinded portion of the Phase 3 Coronavirus Efficacy (COVE) trial. While mRNA-1273 demonstrated high efficacy in prevention of COVID-19, including severe disease, its effect on the viral dynamics of SARS-CoV-2 infections is not understood.

Non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine for the prevention of exacerbations in chronic obstructive pulmonary disease: a multicentre, randomised, placebo-controlled, observer-blinded, proof-of-concept, phase 2b trial.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with changes in the sputum microbiome, including an increased prevalence of pathogenic bacteria. Vaccination against the most frequent bacteria identified in AECOPD might reduce exacerbation frequency. We assessed the efficacy, safety, and immunogenicity of a candidate vaccine containing surface proteins from non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) in patients with COPD.

Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial.

Background: In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids.

Methods: The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.

Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial.

Introduction: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD.

Methods: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS.

A randomized controlled trial of glycopyrrolate administered by metered dose inhaler in patients with uncontrolled asthma despite ICS/LABA treatment.

Objective: To evaluate the efficacy and safety of three doses of glycopyrrolate metered dose inhaler (GP MDI) in patients with uncontrolled asthma despite treatment with inhaled corticosteroid/long-acting β-agonists (ICS/LABA) with or without tiotropium, to characterize the benefit of triple therapy.

Method: This phase II/III, double-blind study randomized patients to 24 weeks' treatment with twice-daily GP MDI 36 µg, 18 µg, 9 µg, or placebo MDI (all delivered Aerosphere inhalers), or once-daily open-label tiotropium 2.5 µg.

Dual Bronchodilator Therapy as First-Line Treatment in Maintenance-Naïve Patients with Symptomatic COPD: A Pre-Specified Analysis of the EMAX Trial.

Introduction: Limited prospective evidence is available to guide selection of first-line maintenance therapy in patients with COPD. This pre-specified analysis of the EMAX trial explored the efficacy and safety of dual- versus mono-bronchodilator therapy in maintenance-naïve and maintenance-treated patients.

Methods: The 24-week EMAX trial evaluated lung function, symptoms (including rescue medication use), exacerbations, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids.

Dose-Ranging and Cumulative Dose Studies of Albuterol Sulfate MDI in Co-Suspension Delivery™ Technology (AS MDI; PT007) in Patients with Asthma: the ASPEN and ANTORA Trials.

Background And Objectives: Co-suspension Delivery™ Technology has been developed for the administration of albuterol sulfate pressurised inhalation suspension via metered-dose inhaler (AS MDI, PT007). We assessed the efficacy and safety of AS MDI versus Proventil in order to determine the optimal dose of AS MDI to take to Phase III clinical trials.

Methods: ASPEN (NCT03371459) and ANTORA (NCT03364608) were Phase II, randomised, crossover, multicentre studies of AS MDI versus Proventil in patients with persistent asthma.

Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2).

Background: These studies assessed the efficacy and safety of fevipiprant, an oral antagonist of the prostaglandin D (PGD) receptor (DP), compared with placebo when added to standard-of-care (SoC) asthma therapy in patients with uncontrolled asthma.

Methods: ZEAL-1 (NCT03215758) and ZEAL-2 (NCT03226392) are two replicate, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies in which fevipiprant 150 mg once daily (o.d.

Treatment of COPD with Long-Acting Bronchodilators: Association Between Early and Longer-Term Clinically Important Improvement.

Introduction: This post hoc analysis of the "Early MAXimization of bronchodilation for improving COPD stability" (EMAX) trial investigated whether patients achieving early clinically important improvement (CII) sustained longer-term improvements and lower risk of clinically important deterioration (CID).

Methods: Patients were randomized to umeclidinium/vilanterol, umeclidinium, or salmeterol for 24 weeks. The patient-reported outcomes (PROs) Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms, St George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) were assessed.

Efficacy and Safety of Inhaled Glycopyrronium Bromide in COPD: A Randomized, Parallel Group, Dose-Ranging Study (GLIMMER).

This Phase II, randomized, parallel group study was conducted as part of US regulatory requirements to identify the most appropriate dose of the long-acting muscarinic antagonist glycopyrronium bromide (GB) for use in a single-inhaler triple-therapy combination with the inhaled corticosteroid beclomethasone dipropionate plus the long-acting β-agonist formoterol fumarate. Eligible subjects were adults with COPD and post-bronchodilator forced expiratory volume in 1 s (FEV) 40-80% predicted. Subjects were randomized to receive inhaled double-blind GB 6.

Impact of baseline COPD symptom severity on the benefit from dual mono-bronchodilators: an analysis of the EMAX randomised controlled trial.

Rationale: Symptom relief is a key treatment goal in patients with chronic obstructive pulmonary disease (COPD). However, there are limited data available on the response to bronchodilator therapy in patients at low risk of exacerbations with different levels of symptom severity. This study compared treatment responses in patients with a range of symptom severities as indicated by baseline COPD assessment test (CAT) scores.

Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

Background: Short-acting β-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD.

Methods: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.

Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial.

Background: Despite inhaled corticosteroid plus long-acting β-agonist (ICS/LABA) therapy, 30-50% of patients with moderate or severe asthma remain inadequately controlled. We investigated the safety and efficacy of single-inhaler fluticasone furoate plus umeclidinium plus vilanterol (FF/UMEC/VI) compared with FF/VI.

Methods: In this double-blind, randomised, parallel-group, phase 3A study (Clinical Study in Asthma Patients Receiving Triple Therapy in a Single Inhaler [CAPTAIN]), participants were recruited from 416 hospitals and primary care centres across 15 countries.

Observational Real-World Study to Assess Clinical Characteristics and Device Satisfaction in Patients with COPD Treated with Glycopyrrolate/eFlow CS.

Purpose: To assess clinical characteristics and device satisfaction of patients with chronic obstructive pulmonary disease (COPD) treated with glycopyrrolate/eFlow Closed System (CS) nebulizer (further referred to as eFlow) under real-world conditions.

Participants And Methods: Patients with COPD currently using eFlow were identified by the study sponsor. Consenting patients who met study inclusion criteria completed a cross-sectional survey that included a device satisfaction questionnaire.

Comparing Randomized Controlled Trials and Real-World Studies in Chronic Obstructive Pulmonary Disease Pharmacotherapy.

Analytic epidemiological studies cover a large spectrum of study methodologies, ranging from noninterventional observational studies (population-based, case-control, or cohort studies) to interventional studies (clinical trials). Herein, we review the different research methodologies or study designs and discuss their advantages and disadvantages in the context of chronic obstructive pulmonary disease (COPD) pharmacotherapy. Although randomized controlled trials (RCTs) are considered the "gold standard" for evaluating the efficacy and safety of an intervention, observational studies conducted in a real-world scenario are useful in providing evidence on the effectiveness of the intervention in clinical practice; understanding both efficacy and effectiveness is important from the clinician's perspective.

A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids.

Background: Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.

Methods: This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.