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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
262
Nebulized 3% hypertonic saline, 5 mL once daily via mesh nebulizer. Administered during Months 0-6 in the early-initiation arm and during Months 4-6 in the delayed-initiation arm after completion of the Month 3 assessment.
Nebulized 0.9% normal saline, 5 mL once daily via mesh nebulizer during Months 0-3 in the delayed-initiation arm.
Taipei Veterans General Hospital
Taipei, Taiwan
RECRUITINGChange in Total Respiratory Severity Score (RSS) From Baseline to Month 3
Total Respiratory Severity Score (RSS) ranges from 0 to 60 and is calculated from six visual analog scales evaluating cough, sputum production, dyspnea, fatigue, sleep disturbance, and overall respiratory symptoms. Higher scores indicate worse symptoms.
Time frame: Baseline and Month 3
Change in Acid-Fast Bacilli (AFB) Sputum Smear Grade Over Time
AFB sputum smear grade assessed using standard semi-quantitative microscopy (negative, scanty, 1+, 2+, 3+, or 4+) at Baseline, Month 3, and Month 6. Changes in smear grade and the proportion of participants achieving smear negativity will be evaluated.
Time frame: Baseline, Month 3, and Month 6
Change in Mycobacterial Sputum Culture Status Over Time
Sputum culture status assessed as positive or negative for nontuberculous mycobacteria using standard mycobacterial culture methods at Baseline, Month 3, and Month 6. Culture conversion is defined as a change from positive at baseline to negative at follow-up assessments.
Time frame: Baseline, Month 3, and Month 6
Change in Radiographic Severity Score From Baseline to Month 6
Radiographic Severity Score assessed using a chest radiographic scoring system. Each lung is divided into three areas. The extent of infiltration in each area is scored from 0 to 3, resulting in a total score ranging from 0 to 18. Higher scores indicate more extensive pulmonary disease.
Time frame: Baseline and Month 6
Change in Erythrocyte Sedimentation Rate (ESR) From Baseline to Month 6
Erythrocyte sedimentation rate (ESR) will be measured using a standard clinical laboratory assay. Higher values indicate greater systemic inflammation.
Time frame: Baseline and Month 6
Change in R5-R20 Measured by Impulse Oscillometry From Baseline to Month 6
R5-R20 measured by impulse oscillometry (IOS). R5 represents total airway resistance and R20 represents central airway resistance. The difference between R5 and R20 (R5-R20) reflects small airway dysfunction. Higher values indicate greater small airway impairment.
Time frame: Baseline and Month 6
Change in Post-Bronchodilator FEV1 (% Predicted) From Baseline to Month 6
Post-bronchodilator forced expiratory volume in one second (FEV1), expressed as percent predicted, measured using standardized spirometry according to ATS/ERS recommendations. Higher values indicate better lung function.
Time frame: Baseline and Month 6
Anti-NTM Treatment Initiation
Proportion of Participants Requiring Anti-NTM Antibiotic Treatment
Time frame: Up to Month 6
Adverse Events
Incidence of Adverse Events Related to Hypertonic Saline Inhalation
Time frame: Up to Month 6
Within-Participant Change in Respiratory Severity Score During Normal Saline and Hypertonic Saline Treatment Periods in the Delayed-Initiation Arm
Comparison of RSS change during Months 0-3 while receiving nebulized normal saline and during Months 4-6 while receiving nebulized 3% hypertonic saline in participants assigned to the delayed-initiation arm.
Time frame: Baseline to Month 6
Change in Respiratory Severity Score From Month 3 to Month 6 in the Early-Initiation Arm
Evaluation of continued symptom improvement after the initial 3 months of hypertonic saline treatment.
Time frame: Month 3 and Month 6
Change in Total RSS at Month 6
Total RSS ranges from 0 to 60 and is calculated from six visual analog scales evaluating cough, sputum production, dyspnea, fatigue, sleep disturbance, and overall respiratory symptoms. Higher scores indicate worse symptoms.
Time frame: Baseline and Month 6
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.