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Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): Two double-blind, parallel-group, randomized, controlled phase 3 trials

The Lancet Nov 13, 2019

Virchow JC, Kuna PK, Paggiaro P, et al. – Researchers conducted two parallel-group, double-blind, randomized, active-controlled, phase 3 trials—Triple in Asthma With Uncontrolled Patients on Medium Strength of ICS + LABA (TRIMARAN) and Triple in Asthma High Strength Vs ICS/LABA HS and Tiotropium (TRIGGER)—involving individuals from over 200 sites across more than 16 countries to compare the efficacy of a single-inhaler triple therapy in asthma. Specifically, they compared the single-inhaler extrafine combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting β 2 agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP with FF. Study participants (aged 18–75 years) had uncontrolled asthma, a history of ≥ 1 exacerbations in the previous year, and were previously treated with inhaled corticosteroid (TRIMARAN: medium dose; TRIGGER: high dose) in addition to a long-acting β2 agonist. Enrolled patients were initially treated with BDP/FF for 2 weeks, then randomized to treatment using an interactive response technology system with a balanced block randomization scheme stratified by country. In TRIMARAN, patients were randomized to 52 weeks of BDP/FF/G or BDP/FF, two inhalations twice daily. In TRIGGER, patients were randomized to 52 weeks of BDP/FF/G or BDP/FF—both two inhalations twice daily—or open-label BDP/FF two inhalations twice daily along with tiotropium 2.5 μg two inhalations once daily. Among patients who received ≥ 1 dose of study treatment, safety was evaluated. Overall, among those with uncontrolled asthma, adding a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting β2-agonist therapy enhanced lung function and decreased aggravations.

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