Hypertonic Saline Inhalation for Mycobacterium Avium Complex Pulmonary Disease

Mycobacterium Avium Complex Clinical Trial

— SALINE  

Official title:

A Randomized Controlled Trial on Hypertonic Saline Inhalation in Patients With Nodular-bronchiectatic Mycobacterium Avium Complex Pulmonary Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05192057
• Other study ID #: KGx60
• Status: Recruiting
• Phase: Phase 4
• Start date: May 20, 2022
• Est. completion date: August 20, 2026

Study information

• Verified date: April 2024
• Source: Radboud University Medical Center
• Contact: Arthur Lemson, MSc
• Phone: +31634265743
• Email: arthur.lemson[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The SALINE trial will investigate the effect of Hypertonic Saline inhalation plus best supportive care on burden of symptoms, clearance of mycobacteria and functional capacities in participants with Mycobacterium avium complex lung disease and compare the effect to treatment with best supportive care alone.

Description:

The treatment of Mycobacterium avium complex (MAC) lung disease consists of best supportive care, often accompanied by long-lasting multi-drug antibiotic regimens. Two major radiologic patterns exist: nodular-bronchiectatic and fibrocavitary disease, characterized by slow and rapid progression of disease, respectively. SALINE is an open-label, randomized, two-arm controlled study that investigates the effect of Hypertonic Saline inhalation (HSi) plus best supportive care versus best supportive care alone for 12 weeks in participants with nodular-bronchiectatic MAC lung disease. The investigators hypothesize that HSi added to best supportive care will improve health-related quality of life and reduce mycobacterial load more than best supportive care alone Participants will be randomized 1:1 to a study arm. Best supportive care comprises of management of a predisposing (lung) condition, guidance in smoking cessation, respiratory physiotherapy (e.g. airway clearance) and nutritional guidance. HSi will be administered two times daily. Antibacterial therapy against other bacterial infections and inhaled corticosteroids are allowed during the study period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 20, 2026
• Est. primary completion date: May 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• International guideline criteria for nodular-bronchiectatic MAC lung disease, i.e. symptomatic, nodular bronchiectatic lesions seen on thorax radiography and =2 positive cultures of the same MAC species or one positive culture from a bronchoalveolar lavage;
• =1 positive MAC sputum cultures must be collected in the previous 4 months;
• Signed and dated patient informed consent.

Exclusion Criteria:

• Fibrocavitary MAC lung disease;
• Antimycobacterial treatment in the last 6 months;
• Previous MAC lung disease treatment failure, defined as persistent culture positivity despite >6 months of guideline-recommended treatment;
• Current clinical relevant asthma or otherwise bronchial hyperresponsiveness that is judged to be a contra-indication for HSi.
• Current HSi use
• Former adverse reaction to HSi (note: former HSi use that was stopped due to a lack of clinical improvement is not an exclusion criterium);
• Hypertonic saline intolerability during the screening test inhalation
• Diagnosis of HIV;
• Diagnosis of Cystic fibrosis (CF);
• Active pulmonary malignancy (primary or metastatic) or any other malignancy requiring chemotherapy or radiotherapy within 6 months before screening or anticipated during the study period;
• Active pulmonary tuberculosis, fungal or nocardial disease requiring treatment
• Current use of chronic systemic corticosteroids at doses of 15 mg/day for more than 3 months
• Prior lung or other solid organ transplant
• Known or suspected current drug or alcohol abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the patient.

Related Conditions & MeSH terms

• Lung Diseases
• Mycobacterium Avium Complex
• Mycobacterium avium-intracellulare Infection
• Mycobacterium Infections
• Nontuberculous Mycobacterial Lung Disease

Intervention

Device:
• Hypertonic Saline inhalation
Hypertonic Saline inhalation is thought to increase mucociliary clearance of the airways

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Center	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in health-related quality of life	Measured by the Quality of Life - Bronchiectasis (QOL-B) with NTM module questionnaire at baseline, after 4, 8 and 12 weeks. The QOL-B asks the participant to subjectively rank their symptoms using a 4 scale base ranging from "a lot of difficulty" to "no difficulty", "always" to "never", "completely true" to "not at all true" and "a lot" to "not at all" for 8 domains: physical/role/emotional/social functioning, vitality, treatment burden, health perception and respiratory symptoms. The NTM-module also asks participants to subjectively rank eating problems, body image, digestive symptoms, and NTM symptoms on a 4 scale base.	12 weeks
Primary	Change in health-related quality of life	Measured by the PROMIS Fatigue 7a short form at baseline, after 4, 8 and 12 weeks. This questionnaire assesses self-reported fatigue over the past seven days on a 5 scale base ranging from never (1) to always (5). The lowest possible raw score (indicating the highest subjective level of fatigue) is 7; and the highest possible raw score (indicating the lowest subjective level of fatigue) is 35.	12 weeks
Secondary	Sputum culture conversion	A conversion from positive sputum cultures at baseline to negative sputum cultures after study treatment, defined by two or more negative sputum cultures sampled a week apart.	12 weeks
Secondary	Change in semi-quantitative culture results	Change in acid fast bacilli (AFB) smear determined by auramine staining	12 weeks
Secondary	Change in semi-quantitative culture results	Change in sputum culture time-to-positivity	12 weeks
Secondary	(Serious) Adverse Events as assessed by CTCAE v5.0	Number and severity of (serious) Adverse Events as assessed by CTCAE	12 weeks
Secondary	Treatment failure	Progression of disease that requires the start of antimycobacterial treatment as per the treating physician's discretion.	12 weeks
Secondary	Change in pulmonary function parameters	Forced expiratory volume in 1 second (FEV1; L), Forced Vital Capacity (FVC; L), Inspiratory Capacity (IC; L), Functional Residual Volume (FRC; L) and Total Lung Capacity (TLC; L).	12 weeks
Secondary	Change in pulmonary function parameters	Tiffeneau index (FEV1/FVC; %)	12 weeks
Secondary	Change in physical function capacity	Change in 6-Minute Walking Distance (6MWD).	12 weeks
Secondary	Change in inflammatory serum biomarkers	Change in C-reactive protein (CRP).	12 weeks
Secondary	Change in inflammatory serum biomarkers	Erythrocyte Sedimentation Rate (ERS)	12 weeks
Secondary	Change in inflammatory serum biomarkers	White blood cell count.	12 weeks
Secondary	Therapy adherence	Self-reported therapy adherence expressed as percentage taken of total HSi administrations.	12 weeks
Secondary	Change in self-reported health status	Change in the Nijmegen Clinical Screening Instrument (NCSI) from baseline to 12 weeks. The NCSI evaluates clinical, social and emotional self-reported measures, serves as a tool for an individualized treatment plan and can be repeated regularly to monitor the treatment effect	12 weeks