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| ID | Type | Description | Link |
|---|---|---|---|
| 114-2314-B-075 -079 | Other Grant/Funding Number | National Science and Technology Council, Taiwan | |
| 2025-02-019A | Other Identifier | Taipei Veterans General Hospital |
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| Name | Class |
|---|---|
| National Science and Technology Council, Taiwan | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early Hypertonic Saline Initiation | Experimental | Participants receive nebulized 3% hypertonic saline (5 mL once daily via mesh nebulizer) for 6 months in addition to standard clinical care. Anti-NTM antibiotic treatment may be initiated at the discretion of the treating physician according to clinical indications. |
|
| Delayed Hypertonic Saline Initiation | Active Comparator | Participants receive nebulized normal saline (5 mL once daily via mesh nebulizer) during Months 0-3, followed by nebulized 3% hypertonic saline during Months 4-6, in addition to standard clinical care. Anti-NTM antibiotic treatment may be initiated at the discretion of the treating physician according to clinical indications. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nebulized 3% Hypertonic Saline | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change 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. | Baseline and Month 3 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Month 3, and Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Chest CT Findings From Baseline to Month 6 | Chest CT findings including bronchiectasis, bronchiolitis (tree-in-bud pattern), nodules, consolidation, and cavitary lesions will be evaluated at baseline and Month 6 by comparison of serial CT scans. | Baseline and Month 6 |
| Serum Carbohydrate Antigen 19-9 (CA19-9) Level |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sheng-Wei Pan, MD, PhD | Contact | +886-2-28717456 | swpan2@vghtpe.gov.tw | |
| Jia-Yih Feng, MD, PhD | Contact | +886-2-28712121 | jyfeng@vghtpe.gov.tw |
| Name | Affiliation | Role |
|---|---|---|
| Sheng-Wei Pan, MD, PhD | Taipei Veterans General Hospital, Taiwan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Taipei Veterans General Hospital | Recruiting | Taipei | 11217 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31000680 | Result | Huiberts A, Zweijpfenning SMH, Pennings LJ, Boeree MJ, van Ingen J, Magis-Escurra C, Hoefsloot W. Outcomes of hypertonic saline inhalation as a treatment modality in nontuberculous mycobacterial pulmonary disease. Eur Respir J. 2019 Jul 11;54(1):1802143. doi: 10.1183/13993003.02143-2018. Print 2019 Jul. No abstract available. | |
| 32628747 |
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| ID | Term |
|---|---|
| D001987 | Bronchiectasis |
| D015270 | Mycobacterium avium-intracellulare Infection |
| D009165 | Mycobacterium Infections, Nontuberculous |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
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| ID | Term |
|---|---|
| D012462 | Saline Solution, Hypertonic |
| ID | Term |
|---|---|
| D006982 | Hypertonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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Participants are randomized in a 1:1 ratio to either early initiation of 3% hypertonic saline inhalation for 6 months or delayed initiation consisting of normal saline inhalation during Months 0-3 followed by 3% hypertonic saline during Months 4-6. The primary comparison is performed at Month 3 between the two parallel groups.
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| Nebulized Normal Saline | Drug | Nebulized 0.9% normal saline, 5 mL once daily via mesh nebulizer during Months 0-3 in the delayed-initiation arm. |
|
| 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. | 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. | 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. | 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. | 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. | Baseline and Month 6 |
| Anti-NTM Treatment Initiation | Proportion of Participants Requiring Anti-NTM Antibiotic Treatment | Up to Month 6 |
| Adverse Events | Incidence of Adverse Events Related to Hypertonic Saline Inhalation | 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. | 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. | 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. | Baseline and Month 6 |
Change in serum carbohydrate antigen 19-9 (CA19-9) concentration from baseline to Months 3 and 6. CA19-9 will be measured using a standard clinical laboratory assay. Higher levels may reflect greater airway inflammation and disease burden in nontuberculous mycobacterial lung disease. |
| Baseline, Month 3 and Month 6 |
| Serum Cancer Antigen 125 (CA125) Level | Change in serum cancer antigen 125 (CA125) concentration from baseline to Months 3 and 6. CA125 will be measured using a standard clinical laboratory assay. Higher levels may reflect greater pulmonary disease activity and extent of bronchiectatic involvement. | Baseline, Month 3 and Month 6 |
| Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, Bottger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL. Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis. 2020 Aug 14;71(4):e1-e36. doi: 10.1093/cid/ciaa241. |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |