Glycopyrrolate/formoterol fumarate MDI in mild-to-moderate chronic obstructive pulmonary disease (PIONEER): a protocol for a randomised, double-blind, placebo-controlled trial.

Abstract

Introduction: Patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) often experience rapid declines in lung function but are rarely treated early. The Prospect of early InterventiON in the managEment of chronic obstructivE pulmonaRy disease (PIONEER) study aims to evaluate the efficacy of long-term glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) as an initial therapy on lung function and disease progression in individuals with mild-to-moderate COPD.

Methods and analysis: This is a multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Approximately 318 patients with COPD in Global Initiative for Chronic Obstructive Lung Disease stages 1 (mild) or 2 (early moderate), with no history of severe exacerbations in the previous year, will be randomised in a 2:1 ratio to receive two times per day GFF MDI (14.4/10 µg) or placebo for 52 weeks. Clinical assessments will include pulmonary function tests, symptom scores, quality-of-life measures, recording of COPD exacerbations and chest CT. The primary endpoint is the between-group difference in the change from baseline in forced expiratory volume in 1 s (FEV₁) after 2 hours of bronchodilator over 24 weeks. Secondary endpoints include the between-group difference in the change from baseline in morning pre-dose trough FEV₁ over 24 weeks, morning post-dose 2 hour FEV₁ over 52 weeks and time to minimal clinically important deterioration. The safety endpoint is the incidence of adverse events. An extension study with rerandomisation will follow the PIONEER study to explore the long-term need for GFF MDI use.

Trial registration number: ChiCTR2200064765; Chinese Clinical Trial Registry, www.chictr.org.cn.

Ethics and dissemination: The study protocol has been approved by the Ethics Committee of The First Affiliated Hospital, Guangzhou Medical University (2022-23、2024-K-005), and all collaborating centres have obtained approval from their respective ethics committees. Results will be presented at national and international meetings and submitted for publication in peer-reviewed journals within the field.