Safety and tolerability of the low global warming potential propellant HFA-152a in patients with asthma receiving beclometasone dipropionate/formoterol fumarate/glycopyrronium: The TRECOS study

Respir Med. 2026 May:256:108814. doi: 10.1016/j.rmed.2026.108814. Epub 2026 Apr 6.

Abstract

Background: Propellants currently used in pressurised metered-dose inhalers (e.g., HFA-134a) are being replaced by low global warming potential alternatives, including HFA-152a. This study aimed to assess the bronchoconstriction potential and the safety and tolerability of triple combination beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) HFA-152a pMDI compared to BDP/FF/G HFA-134a pMDI.

Methods: Adults with moderate-to-severe controlled asthma received BDP/FF/G HFA-134a pMDI for a two-week run-in, then were randomised 1:2 to either continue the HFA-134a pMDI formulation or switch to the HFA-152a pMDI formulation, both for 12 weeks. The primary objective was to compare the bronchoconstriction potential of BDP/FF/G HFA-152a vs HFA-134a in terms of the relative change from pre-dose in forced expiratory volume in 1 s (FEV1) at 10 min post-dose on Day 1. Safety and tolerability assessments included adverse event occurrence.

Results: Of 553 patients randomised to treatment, 539 (97.5%) completed the study (356/368 [96.7%] and 183/185 [98.9%] with the HFA-152a and HFA-134a formulations, respectively). There was no difference between the two groups for the primary endpoint, with an adjusted mean (95% confidence interval) HFA-152a vs HFA-134a difference of -1.143% (-2.769%, 0.483%). A total of 19.3% patients experienced adverse events with the HFA-152a formulation (71/368) compared to 27.6% with the HFA-134a formulation (51/185); most events with both formulations were mild or moderate in severity.

Conclusions: Overall, transitioning to the low global warming potential HFA-152a formulation had no impact on the safety and tolerability of BDP/FF/G, with the positive effect on lung function comparable to the original HFA-134a formulation.

Keywords: Asthma; Bronchoconstriction; Climate change; Formulation; Propellant; Triple therapy.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aerosol Propellants* / administration & dosage
  • Aerosol Propellants* / adverse effects
  • Aged
  • Anti-Asthmatic Agents* / administration & dosage
  • Anti-Asthmatic Agents* / adverse effects
  • Anti-Asthmatic Agents* / therapeutic use
  • Asthma* / drug therapy
  • Asthma* / physiopathology
  • Beclomethasone* / administration & dosage
  • Beclomethasone* / adverse effects
  • Beclomethasone* / therapeutic use
  • Bronchoconstriction / drug effects
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Drug Combinations
  • Ethanolamines / administration & dosage
  • Ethanolamines / adverse effects
  • Female
  • Fluorocarbons
  • Forced Expiratory Volume / drug effects
  • Formoterol Fumarate* / administration & dosage
  • Formoterol Fumarate* / adverse effects
  • Glycopyrrolate* / administration & dosage
  • Glycopyrrolate* / adverse effects
  • Glycopyrrolate* / therapeutic use
  • Humans
  • Hydrocarbons, Fluorinated* / administration & dosage
  • Hydrocarbons, Fluorinated* / adverse effects
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Treatment Outcome

Substances

  • Beclomethasone
  • Formoterol Fumarate
  • Fluorocarbons
  • Drug Combinations
  • Aerosol Propellants
  • Glycopyrrolate
  • Hydrocarbons, Fluorinated
  • apaflurane
  • Bronchodilator Agents
  • Anti-Asthmatic Agents
  • Ethanolamines