Clinical trial NCT06568445: Maintenance at Initial Treatment With Sequential Anti-Inflammation Reliever Therapy
Official title: Efficacy of Regular ICS/LABA Sequential As-Needed Therapy in Newly Diagnosed Mild Asthma Patients: A Randomized, Parallel, Positive-Control Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Bronchial Asthma
Keywords: asthma
budesonide-formoterol
Lead sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2024-08-23
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. Evaluate the efficacy of 4 weeks of maintenance therapy with low-dose ICS/LABA versus as-needed low-dose ICS/LABA in newly diagnosed mild asthma patients. Assess the improvement in FEV1 from baseline over 4 weeks, and the impact on airway reversibility and inflammation levels. Identify the optimal patient population and treatment regimen for the medication.
2. Based on a comprehensive evaluation of pulmonary function parameters (including large airway parameters: FEV1, FEV1/FVC; peak flow: PEF; small airway parameters: FEF25%, FEF50%, FEF75%, MMEF) and airway inflammation levels, explore biomarkers that can effectively predict the efficacy of maintenance therapy with low-dose ICS/LABA in newly diagnosed mild asthma patients.
3. Compare 4 weeks of initial maintenance therapy with low-dose ICS/LABA followed by as-needed low-dose ICS/LABA therapy until 24 weeks. In the 24-week study, incorporate mobile lung function monitoring to dynamically assess large and small airway function parameters and clinical indicators. Explore the impact of early maintenance therapy with low-dose ICS/LABA followed by as-needed treatment on FEV1 improvement from baseline, acute exacerbation risk indicators, and airway inflammation, and develop a model to predict acute exacerbations.

Detailed description: After being informed about the study and potential risks, all patients giving written informed consent will undergo a 1-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a 1:1 ratio to research group (maintenance at initial treatment sequential as-needed therapy group) and control group (As-needed therapy group).

Eligibility criteria: Inclusion Criteria:

1. Participants fully understand the purpose and methods of the study, voluntarily agree to participate, and sign an informed consent form before any study procedures begin.
2. Adults (including males and non-pregnant, non-lactating females) aged 18 to 70 years (inclusive), who are newly diagnosed with mild and non-acute bronchial asthma according to the latest Chinese guidelines for the prevention and treatment of bronchial asthma.
3. During the screening period, participants must meet at least one of the following criteria for reversible airflow obstruction: Positive bronchodilator test (increase in FEV1 ≥12% and an absolute increase in FEV1 ≥200 mL after inhaling a bronchodilator). Positive bronchial provocation test (FEV1 decreases by ≥20% after inhalation of the provocation agent methacholine).
4. At screening and the Day -1 visit before the induction period, participants must have a lung function test showing FEV1 ≥ 80% of the predicted value.
5. Participants or their guardians must be able to communicate effectively with the researchers, understand, and comply with all requirements of the study.

Exclusion Criteria:

1. Individuals allergic or intolerant to budesonide, formoterol, albuterol, or any component of the medication.
2. Respiratory, sinus, or middle ear infections within the 2 months prior to screening or up to randomization that led to a change in asthma treatment, or are expected to alter the participant's asthma status according to the investigator's judgment.
3. History of chronic obstructive pulmonary disease (COPD), interstitial lung disease, restrictive lung disease, tuberculosis, cystic fibrosis, bronchiectasis, or alpha-1 antitrypsin deficiency at screening.
4. History of major diseases at screening, such as congestive heart failure, uncontrolled hypertension, severe coronary artery disease, myocardial infarction, or severe arrhythmias, or severe hematological, hepatic, neurological, musculoskeletal, endocrine, metabolic, psychiatric, renal, or other significant conditions. If any of these conditions worsen during the study, it may endanger the participant or affect study results.
5. Excessive use of short-acting beta-agonists (SABA), defined as more than 8 inhalations per day, during the screening period and the run-in period.
6. Use of beta-blockers (including eye drops), oral corticosteroids, systemic steroid treatments, investigational drugs, or leukotriene receptor antagonists (such as zafirlukast, pranlukast, montelukast, etc.) during the run-in period.
7. History of smoking with a smoking index \>10 pack-years.
8. Smoking cessation ≤6 months before the screening visit (Visit 1) or current smokers.
9. Known or suspected alcohol and/or drug abuse, including heavy drinking (average daily consumption \>2 units of alcohol, where 1 unit = 360 mL of beer, 45 mL of 40% alcohol, or 150 mL of wine).
10. Abnormal and clinically significant results in vital signs, physical examination, 12-lead ECG, chest CT, blood tests, urinalysis, blood biochemistry, or coagulation tests at screening and the Day -1 visit, unless judged by the investigator to be related to the study condition and not affecting inclusion.
11. Pregnant or breastfeeding females.
12. Use of medications that may interact with the study drug within 1 month before screening, such as CYP3A4 inhibitors (e.g., ketoconazole, itraconazole), cimetidine, disulfiram, metronidazole, or CYP3A4 enzyme inducers (e.g., rifampin, carbamazepine, phenytoin).
13. Participation in other medical device clinical trials within 1 month before screening or other drug clinical trials within 3 months before screening.
14. Asthma total symptom score (daytime + nighttime) \<2 points in the week prior to randomization.
15. Patients who cannot comply with the study procedures or who, in the investigator's judgment, are not suitable for participation in the study.

Primary outcomes:
measure: Change from baseline in forced expiratory volume in the first second (FEV1) at week 4
timeFrame: Baseline and Week 4
Secondary outcomes:
measure: Change from baseline in forced expiratory volume in the first second (FEV1) at Week 8, 12, 16, 20, 24
timeFrame: Baseline and Week 8, 12, 16, 20, 24
measure: Change from baseline in Asthma control test (ACT) scrore
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
measure: Change from baseline in Asthma control questionnaire-5 (ACQ-5)
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
measure: Change from baseline in Fractional exhaled nitric oxide (FENO)
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
measure: Change from baseline in Eosinophil counts in peripheral blood
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
measure: Change from baseline in Induced sputum classification and counting
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
measure: Acute exacerbation of bronchial asthma
timeFrame: Week 4, 8, 12, 16, 20, 24
measure: Change from baseline in Forced Expiratory Flow at between 25% and 75% (FEF25%-75%)
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 24
Other outcomes:
measure: Adverse events
timeFrame: Week 4, 8, 12, 16, 20, 24
Locations:
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
Study officials:
affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Yan Zhou
role: PRINCIPAL_INVESTIGATOR
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