Overview
This multicenter randomized controlled trial evaluates the clinical and microbiological effects of inhaled 3% hypertonic saline in treatment-naïve patients with nontuberculous mycobacterial lung disease (NTM-LD). Participants are randomized in a 1:1 ratio to either early initiation of 3% hypertonic saline for 6 months or delayed initiation consisting of normal saline inhalation during the first 3 months followed by 3% hypertonic saline during the subsequent 3 months.
The primary objective is to compare respiratory symptom improvement between hypertonic saline and normal saline at Month 3. Secondary objectives include evaluating sputum microbiological outcomes, radiographic changes, inflammatory markers, small airway function, treatment initiation, safety, and within-participant changes before and after switching from normal saline to hypertonic saline in the delayed-initiation arm.
The first participant was enrolled on October 3, 2025.
Description
Nontuberculous mycobacterial lung disease (NTM-LD) is a chronic pulmonary infection that frequently progresses despite conservative management. Because prolonged multidrug antibiotic therapy is associated with substantial treatment burden, potential toxicity, and variable effectiveness, additional non-antibiotic treatment strategies are needed, particularly for patients who defer, cannot tolerate, or are not yet indicated for antibiotic treatment.
Hypertonic saline inhalation facilitates airway clearance and sputum removal and has been increasingly used as an adjunctive treatment in specialized NTM centers. However, prospective randomized data remain limited, particularly in Asian populations.
This multicenter randomized controlled trial investigates whether early initiation of inhaled 3% hypertonic saline improves respiratory symptoms and microbiological outcomes compared with delayed initiation.
To ensure treatment safety, all participants undergo a supervised inhalation tolerance assessment before randomization. During this assessment, inhaled salbutamol (Ventolin) premedication is administered, followed by inhalation of 3% hypertonic saline. Participants demonstrating clinically significant intolerance, severe bronchospasm, or other safety concerns are excluded from study treatment.
Following successful completion of the tolerance assessment, participants are randomized to one of two groups.
The early-initiation group receives inhaled 3% hypertonic saline for 6 months. The delayed-initiation group receives inhaled normal saline during Months 0-3, followed by inhaled 3% hypertonic saline during Months 4-6.
The primary randomized comparison is performed at Month 3 between participants receiving hypertonic saline and those receiving normal saline. Additional analyses evaluate within-participant changes in the delayed-initiation arm before and after switching from normal saline to hypertonic saline.
Throughout the study, participants continue routine clinical care. Initiation of anti-NTM antibiotic treatment remains at the discretion of the treating physician.
Eligibility
Inclusion Criteria:
- Adults aged 18 years or older.
- Diagnosis of nontuberculous mycobacterial lung disease (NTM-LD) according to ATS/ERS/ESCMID/IDSA diagnostic criteria, including compatible clinical symptoms, radiographic findings, and microbiological evidence.
- Not receiving anti-NTM antibiotic treatment at the time of screening.
- Able and willing to provide written informed consent.
- Able to perform nebulized inhalation therapy using a mesh nebulizer at home.
Exclusion Criteria:
- Active tuberculosis.
- Human immunodeficiency virus (HIV) infection.
- Receiving active treatment for malignancy.
- Uncontrolled asthma.
- Frequent or clinically significant hemoptysis.
- History of intolerance, bronchospasm, or hypersensitivity during inhalation testing with hypertonic saline.
- Inability to prepare a mesh nebulizer or perform inhalation therapy at home.
- Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study participation.
