Three-in-One Inhaler Found to Improve Lung Function, Reduce Asthma Attacks in 2 Phase 3 Trials

Research presented at the European Respiratory Society Conference 2019 details the novel use of a single inhaler combining 3 therapies, as opposed to 2, in 2 clinical studies on patients with severe asthma.

Patients with severe asthma may potentially benefit from using a novel single inhaler treatment combining 3 therapies as opposed to 2, based off research from 2 phase 3 trials published this week in The Lancet and simultaneously presented at the European Respiratory Society (ERS) Conference 2019.1

Multiple inhaler use is correlated to reducing a patient’s ability to administer treatment regularly as prescribed. As patients with severe asthma often have to use devices of different design, different instructions, and different dosing regimens, this process can inhibit the effective prevention of symptoms related to their condition.

Researchers sought to investigate the use of a single inhaler that combines therapies to potentially ensure effective treatment delivery and improved treatment adherence. Previously, a trial of 3 medicines being administered through 2 separate inhalers indicated a significant improvement in lung function, as well as a reduction in asthma attacks and symptoms in patients with severe asthma.

The study examined the efficacy of an innovative 3-in-1 inhaler therapy in 2 parallel-group, double-blind, randomized, active-controlled, phase 3 trials with a combined 2592 patients across 17 countries. The studies, known as TRIMARAN and TRIGGER, trialled 2 different strengths of the triple therapy (TRIMARAN: medium dose; TRIGGER: high dose) in patients with uncontrolled asthma from 2016 to 2018.

Both therapies included a steroid preventer known as beclomethasone dipropionate (BDP; inhaled corticosteroid), a long-acting bronchodilator (β2) agonist known as formoterol fumarate (FF), and a long-acting muscarinic antagonist (LAMA) called glycopyrronium (G) with the combination of BDP and FF. Enrolled patients were initially treated with BDP/FF (TRIMARAN: 100 mcg BDP and 6 mcg FF; TRIGGER: 200 mcg BDP and 6 mcg FF) for 2 weeks. Patients, investigators, site staff, and sponsor staff were then masked to BDP/FF/G and BDP/FF assignment:

  • TRIMARAN patients were randomly assigned to 52 weeks of BDP/FF/G (100 mcg BDP, 6 mcg FF, and 10 mcg G; 579 patients) or BDP/FF (100 mcg BDP and 6 mcg FF; 576 patients) for 2 inhalations administered twice daily
  • TRIGGER patients were randomly assigned to 52 weeks of BDP/FF/G (200 mcg BDP, 6 mcg FF, and 10 mcg G; 573 patients) or BDP/FF (200 mcg BDP and 6 mcg FF; 576 patients) for 2 inhalations twice daily, or open-label BDP/FF (200 mcg BDP, 6 mcg FF; 288 patients) for 2 inhalations twice daily with 2.5 mcg of tiotropium for 2 inhalations once daily

The outcomes measured in the study were lung function and whether moderate or more severe asthma attacks persisted in patients. Forced expiratory volume (FEV1) was used to test lung function, or the degree to which patients’ airways were obstructed, by the volume in milliliters (mL) derived from having patients exhale as much air as they could in a second.

Study results revealed that when compared with the BDP/FF group, the 3-in-1 inhaler therapy (BDP/FF/G) improved week 26 predose FEV1 by 57 mL (95% CI, 15-99; P = .0080) in TRIMARAN and by 73 mL (95% CI, 26-120; P = .0025) in TRIGGER. For the rate of moderate and severe exacerbations, TRIMARAN participants exhibited reductions of 15% (rate ratio [RR] = 0.85; 95% CI, 0.73-0.99; P = .033) and TRIGGER participants showed reductions of 12% (RR = 0.88; 95% CI, 0.75-1.03; P = .11).

The addition of a LAMA to the combination of inhaled corticosteroid and long-acting β2 antagonist therapy showed a definite improvement in lung function and exacerbation reduction in the study.

Lead study author J. Christian Virchow, MD, head of the Department of Pneumology and Intensive Care Medicine at the Rostock University Medical Center, stressed the importance of each improvement in asthma care, especially in patients with more severe symptoms. “The effects of triple therapy might seem moderate when you look at the numbers involved, but even incremental improvements can be valuable when there are few treatment options left available,” said Virchow.

In an accompanying commentary,2 Mark Fitzgerald, MD, head of the respiratory medicine division at the University of British Columbia, embraced the new treatment option while additionally pushing for increased research into respiratory medications. “We need to continue to improve characterization of the heterogeneous nature of airway diseases and in parallel employ targeted treatments for the right patient at the appropriate time,” he said.


  1. Virchow JC, Kuna P, Paggiaro P, et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER). [published online September 30, 2019]. Lancet. doi: 10.1016/S0140-6736(19)32215-9.
  2. Fitzgerald JM, Sadatsafavi M. Triple therapy in a single inhaler: a new option for uncontrolled asthma. [published online September 30, 2019]. Lancet. doi: 10.1016/S0140-6736(19)32216-0.
Related Videos
View All
Related Content
© 2023 MJH Life Sciences
All rights reserved.