Impact of GDMT in Uncontrolled Asthma Patients Receiving MHD Inhaled Corticosteroids + Long-acting β2 Agonist

This study is a prospective, multicenter, cluster-randomized trial conducted in China, designed to evaluate the application effect of Guideline-Directed Medical Therapy (GDMT). A scientific committee will be established to be responsible for developing GDMT educational materials and facilitating the implementation of GDMT. The study will introduce a GDMT pathway in intervention group aimed at guiding physicians and specialized nurses in the diagnosis and management of participants who are receiving medium- to high-dose ICS-LABA therapy but have uncontrolled asthma.

This study plans to include approximately 60 study sites and consecutively recruit approximately 540 participants. These sites will cover as many provinces and cities as possible to balance geographical distribution. For the 60 selected sites meeting the hospital qualification requirements, a stratified block randomization method will be used, with the stratification factor being the prior written diagnosis rate for severe asthma (the proportion of severe asthma written diagnoses among patients with asthma on medium-to-high dose ICS-LABA). Sites will be randomly allocated in a 1:1 ratio to either the intervention group or the control group (30 sites per group). To minimize selection bias, each site will consecutively enroll 9 participants who meet all inclusion criteria and have provided signed informed consent. All participants must complete the baseline study assessments before entering the study. This is a cluster-randomized interventional study, with an expected duration of 48 weeks. The intervention is implemented at the hospital level. Participants in the two groups will be managed as follows:

• Intervention Group: Physicians at the study sites will receive GDMT-related training and manage participants according to the GDMT diagnosis and treatment pathway.
• Control Group: Physicians at the study sites will manage participants using usual clinical care.

Participant data (including but not limited to: demographic characteristics, number of exacerbations, asthma medication use, ACT scores, pulmonary function, SGRQ scores, medical costs) will be collected according to the Schedule of Study Activities.

The benefits and effectiveness of GDMT will be determined by assessing changes in physician behavior, improvements in patient outcomes, and savings in healthcare resources.

The intervention consists of 5 distinct components: routine training, GDMT education, clinical monitoring, targeted training, and material revision.

Inclusion criteria

• Sign the informed consent form before any study-related procedures;
• Age 18-75 years (inclusive) at Visit 0;
• Have a written diagnosis of asthma for more than 6 months prior to Visit 0, and have evidence of reversible airflow limitation prior to Visit 0. Evidence of reversible airflow limitation includes: post-bronchodilator increase in Forced Expiratory Volume in 1 second (FEV1) of ≥12% and an absolute increase of ≥200 mL, or average daily diurnal Peak Expiratory Flow (PEF) variability >10%, or an increase in FEV1 of ≥12% and an absolute increase of ≥200 mL compared to baseline after 4 weeks of treatment containing ICS, or a positive bronchial provocation test record. If no prior record exists, reversible airflow limitation must be confirmed and documented via a bronchodilator test during Visit 0;
• Under the usage of MD/HD ICS-LABA;
• Experienced one or more exacerbations within the past year;

Exacerbation is defined as meeting any of the following criteria:

• Use of systemic corticosteroids (or a temporary increase in the stable dose of baseline oral corticosteroids) for at least 3 days; a single injection of a depot long-acting corticosteroid can be considered equivalent to a 3-day course of systemic corticosteroids;
• An emergency department or urgent care site visit for asthma (defined as being evaluated and treated in the emergency department or urgent care site for < 24 hours) requiring the use of systemic corticosteroids for at least 3 days (as described above);
• Hospitalization for asthma (defined as admission to a hospital and/or being evaluated and treated in a healthcare facility for ≥ 24 hours).

Exclusion criteria

• Previous written diagnosis as "Severe Asthma"; Diagnosis of Severe Asthma includes: severe asthma, or related diagnoses containing "severe asthma", or "bronchial asthma (severe)".
• Imaging suggests the presence of bullae or cystic bronchiectasis;
• Currently participating in other interventional studies;
• Previous use of biologics for asthma treatment;
• Using systemic glucocorticoids for other diseases;
• History of respiratory tract infection within 4 weeks prior to Visit 0 (upper respiratory tract infections and lower respiratory tract infections);
• Any significant disease or disorder (e.g., cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, endocrine/metabolic, malignant, psychiatric, or significant physical impairment, etc.) which, in the opinion of the investigator, may put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to comply with GDMT.