Hypertonic Saline Inhalation for Mycobacterium Avium Complex Pulmonary Disease (SALINE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nontuberculous Mycobacterial Lung Disease; Mycobacterium Avium Complex
• Intervention / Treatment: Device: Hypertonic Saline inhalation

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Arthur Lemson, MSc; Phone Number: +31634265743; Email: arthur.lemson@radboudumc.nl
• Study Contact Backup: Name: Wouter Hoefsloot, MSc, PhD; Phone Number: +31612569107; Email: wouter.hoefsloot@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6225GA
    • Recruiting
    • Radboud University Medical Center
    • Contact: Arthur Lemson, MD; Phone Number: +31634265743; Email: arthur.lemson@radboudumc.nl
    • Contact: Wouter Hoefsloot, MD, PhD; Phone Number: +31611072569; Email: wouter.hoefsloot@radboudumc.nl
    • Sub-Investigator: Arthur Lemson, MD
    • Principal Investigator: Wouter Hoefsloot, MD, PhD
    • Principal Investigator: Martin Boeree, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypertonic Saline inhalation; Participants randomized to the Hypertonic Saline inhalation arm will be prescribed a nebulizer for Hypertonic Saline Inhalation (5ml, 5.8%) two times a day for 12 weeks. Participants will also receive best supportive care for 12 weeks (see below).	Device: Hypertonic Saline inhalation; Hypertonic Saline inhalation is thought to increase mucociliary clearance of the airways
No Intervention: Best supportive care; Participants randomized to the best supportive care arm will receive standard of care including management of predisposing (lung) disease, guidance in smoking cessation, respiratory physiotherapy (e.g. airway clearance), nutritional guidance, but no antimycobacterial treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in semi-quantitative culture results	Change in acid fast bacilli (AFB) smear determined by auramine staining	12 weeks
Change in semi-quantitative culture results	Change in sputum culture time-to-positivity	12 weeks
(Serious) Adverse Events as assessed by CTCAE v5.0	Number and severity of (serious) Adverse Events as assessed by CTCAE	12 weeks
Treatment failure	Progression of disease that requires the start of antimycobacterial treatment as per the treating physician's discretion.	12 weeks
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
Change in pulmonary function parameters	Tiffeneau index (FEV1/FVC; %)	12 weeks
Change in physical function capacity	Change in 6-Minute Walking Distance (6MWD).	12 weeks
Change in inflammatory serum biomarkers	Change in C-reactive protein (CRP).	12 weeks
Change in inflammatory serum biomarkers	Erythrocyte Sedimentation Rate (ERS)	12 weeks
Change in inflammatory serum biomarkers	White blood cell count.	12 weeks
Therapy adherence	Self-reported therapy adherence expressed as percentage taken of total HSi administrations.	12 weeks
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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): August 20, 2026

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Lung Diseases; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection
• Other Study ID Numbers: KGx60

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No