An Exploratory Study on Triple Inhaler Therapy in Patients With Early Lung Function Impairment (BGF-PRISm)

Efficacy Evaluation of Budesonide/Glycopyrronium Bromide/Formoterol Inhalation Aerosol in Symptomatic Preserved Ratio Impaired Spirometry (PRISm): A Single-arm Multicenter Clinical Trial

Preserved Ratio Impaired Spirometry (PRISm) is characterized by a normal forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio but an FEV1 below 80% of the predicted value. It has a population prevalence of approximately 10% and is associated with marked symptoms, a high risk of acute exacerbations, and increased mortality. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines PRISm as a pre-chronic obstructive pulmonary disease (COPD) state, and 20%-30% of patients with PRISm will progress to COPD. Currently, no evidence-based therapy exists for PRISm; management is mainly symptomatic relief, and there is an urgent need for evidence-based support. This single-arm clinical trial preliminarily evaluates the efficacy and safety of budesonide/glycopyrronium/formoterol inhalation aerosol in symptomatic patients with PRISm. Symptomatic smokers who meet the diagnostic criteria for PRISm and have an FEV1/FVC ratio ≥0.7 and <0.8 are enrolled and treated with budesonide/glycopyrronium/formoterol inhalation therapy for 12 weeks. The primary endpoint is the change from baseline in FEV1; secondary endpoints include symptom score (COPD Assessment Test, CAT) and quality of life (St George's Respiratory Questionnaire, SGRQ); safety is assessed by recording adverse events (e.g., cardiovascular events); and exploratory analyses examine the association between biomarkers (e.g., peripheral blood eosinophil count, serum IgE level) and treatment efficacy. The study aims to preliminarily explore the efficacy and safety of budesonide/glycopyrronium/formoterol inhaler therapy for PRISm. Early intervention may delay the progression from PRISm to COPD, reduce the burden of chronic respiratory disease, and have important clinical translational value and public health significance.

Study Overview

• Status: Not yet recruiting
• Conditions: Preserved Ratio Impaired Spirometry (PRISM)
• Intervention / Treatment: Drug: Budesonide/glycopyrronium bromide/formoterol inhalation aerosol

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 40-75 years;
2. Smoking history ≥10 pack-years;
3. Pulmonary function test showing 0.7 ≤ FEV1/FVC < 0.8 and FEV1 < 80% predicted;
4. Presence of at least one chronic respiratory symptom (e.g., cough, sputum, dyspnea) lasting ≥3 months;
5. Voluntarily sign a written informed consent form, be able to understand the study objectives, and comply with follow-up requirements;
6. The investigator assesses that the subject is able to complete the 12-week treatment and follow-up and has good medication adherence.

Exclusion Criteria:

1. Concomitant Respiratory Diseases: (1) Diagnosed asthma, bronchiectasis, interstitial lung disease, active tuberculosis, or lung cancer. (2) Meeting the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (post-bronchodilator FEV1/FVC < 0.7). (3) Acute respiratory infection or exacerbation within 4 weeks prior to enrollment.
2. Cardiovascular Disease Risks: (1) Uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg). (2) Myocardial infarction, unstable angina, malignant arrhythmia, or cardiac insufficiency (NYHA class ≥III) within the past 6 months. (3) Long-term use of beta-blockers or antiarrhythmic drugs.
3. Drug-Related Contraindications: (1) Allergy to budesonide, glycopyrronium bromide, formoterol, or excipients of the inhalation aerosol. (2) Use of long-acting bronchodilators (LABA, LAMA), inhaled corticosteroids, or immunosuppressants within 4 weeks prior to enrollment.
4. Other Systemic Diseases: (1) Severe hepatic or renal insufficiency (ALT/AST > 3 times the upper limit of normal, or eGFR < 30 mL/min/1.73m²). (2) Uncontrolled diabetes (HbA1c > 9%) or hyperthyroidism.
5. Special Populations and Compliance Issues: (1) Pregnant or lactating women, or women planning pregnancy without using effective contraception. (2) History of substance abuse, psychiatric disorders, or cognitive impairment that may affect study compliance. (3) The investigator deems the subject unsuitable for participation for other reasons (e.g., life expectancy < 1 year, inability to complete follow-up).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Budesonide/Glycopyrronium Bromide/Formoterol; budesonide/glycopyrronium bromide/formoterol inhalation aerosol

Drug: Budesonide/glycopyrronium bromide/formoterol inhalation aerosol; Budesonide/glycopyrronium/formoterol inhalation aerosol delivers budesonide (160 μg), glycopyrronium (7.2 μg), and formoterol (4.8 μg) per actuation. It is administered as two inhalations twice daily (two in the morning and two in the evening), approximately 12 hours apart, via a pressurized metered-dose inhaler (pMDI). Subjects are required to receive standardized training on inhalation technique to ensure proper technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough forced expiratory volume in the first second (trough FEV1)	Pulmonary function tests will be conducted using standardized spirometry (in accordance with ATS/ERS guidelines) at 12 hours post-dose (trough state).	Baseline, Week 6, and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Saint George's Respiratory Questionnaire (SGRQ) Score	The standardized SGRQ (Chinese version) will be self-administered by the subjects.	Baseline, Week 6, and Week 12
COPD Assessment Test (CAT) Score	The standardized CAT questionnaire (Chinese version) will be self-administered by the subjects.	Baseline, Week 6, and Week 12
Adverse events (AEs) and serious adverse events (SAEs)	All AE/SAE occurrences and types during the treatment period will be recorded. Grading will be performed according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Causality and severity will be assessed by the investigator.	Baseline, Week 6, and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between biomarkers (such as peripheral blood eosinophil count and serum IgE level) and treatment efficacy	Stratify by baseline peripheral blood eosinophil (EOS) count:(i) EOS <100/μL(ii) EOS ≥100 to <300/μL(iii) EOS ≥300/μLAssess the improvement in trough FEV1 according to EOS count level.; Stratify by serum IgE level:(i) IgE > upper limit of normal (ULN)(ii) IgE normalAssess the improvement in trough FEV1 according to IgE level.	Baseline, Week 6, and Week 12

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Preserved Ratio Impaired Spirometry (PRISM)
• Additional Relevant MeSH Terms: Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; Budesonide
• Other Study ID Numbers: SYSKY-2026-195-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No