Hypertonic Saline for Nontuberculous Mycobacterial Lung Disease

Recruiting at 2 trial locations

Overseen By Alyssa Schroeder

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Oregon Health and Science University

Must not be taking: Bedaquiline, Macrolide, Ethambutol, Rifampin

Disqualifiers: HIV, Cystic fibrosis, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether hypertonic saline, a saltwater solution, can help clear lung infections caused by M. avium complex, a type of bacteria. Participants will either use hypertonic saline with a nebulizer or follow the usual treatment guidelines for this condition. It is suitable for individuals who have had two or more positive M. avium complex sputum tests in the past year and have bronchiectasis, a condition that causes widened airways in the lungs. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you have not taken certain medications for MAC treatment, like bedaquiline or a combination of macrolide, ethambutol, and rifampin, in the past 6 months. If you are currently on these medications, you would need to stop them to participate.

What is the safety track record for these treatments?

Research has shown that hypertonic saline is usually safe for treating various lung conditions. While specific evidence for its safety in treating nontuberculous mycobacterial lung disease is lacking, its common use in conditions like cystic fibrosis suggests it might be safe for similar applications.

In studies for other conditions, some participants experienced mild side effects such as throat irritation or coughing. For this trial, if the 7% solution proves too strong, a milder 3% solution is available, which may be easier for some individuals to tolerate.

Overall, hypertonic saline has a history of safety in different lung treatments, providing some confidence in its use for this trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using hypertonic saline for nontuberculous mycobacterial lung disease because it offers a unique approach by harnessing a simple, yet powerful, method of airway clearance. Unlike standard treatments that typically involve antibiotics like azithromycin, ethambutol, and rifampin, hypertonic saline is administered via a nebulizer, directly targeting the lungs to help clear mucus and improve breathing. This delivery method could provide relief more quickly and with fewer side effects, making it a promising addition to existing therapies. Additionally, the ability to adjust the concentration of the saline solution offers flexibility for patients who may not tolerate higher concentrations well.

What evidence suggests that this trial's treatments could be effective for nontuberculous mycobacterial lung disease?

Research shows that a saltwater solution called hypertonic saline can help clear mucus and improve symptoms in people with lung infections caused by Mycobacterium avium complex (MAC). Earlier studies found that this solution can kill and stop the growth of these bacteria in lab tests. In this trial, participants in the hypertonic saline arm will inhale this saline solution, which may help them clear their airways more easily and manage the infection. Since this treatment has already proven effective for at least one condition, its potential benefit in treating MAC lung disease offers hope. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with M. avium complex lung infections who meet specific lung disease criteria and have had at least two positive MAC sputum cultures in the past year. It's not for those with HIV, cystic fibrosis, certain NTM diseases, active tuberculosis or fungal infections, high-dose steroid users, organ transplant recipients, or anyone unable to consent.

Inclusion Criteria

Ability to provide informed consent

You have symptoms that match the guidelines for diagnosing lung diseases set by the American Thoracic Society and Infectious Disease Society of America in 2007.

I have had at least 2 positive lung infection tests in the last year.

Exclusion Criteria

I have been taking more than 15 mg/day of corticosteroids for over 3 months.

I have been diagnosed with HIV.

I have been diagnosed with Cystic Fibrosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either hypertonic saline or standard of care for 12 weeks. The treatment group takes inhaled hypertonic saline twice daily.

12 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including final visit, sputum collection, and AE assessment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azithromycin
• Ethambutol
• Hypertonic Saline
• Rifampin

Trial Overview The study examines if inhaling hypertonic saline can help reduce symptoms and improve mycobacteria clearance in patients with M. avium complex lung disease. Participants will also receive standard treatments like Azithromycin, Ethambutol, and Rifampin.

How Is the Trial Designed?

Group I: Hypertonic saline Experimental Treatment 1 Intervention

Patients who randomize to the hypertonic saline arm will be prescribed a nebulizer device to nebulize hypertonic saline (7%) twice daily for 12 weeks. Hypertonic saline (3%) can be prescribed in the case of poor tolerability of the 7% solution.

Group II: Standard of Care Active Control 3 Interventions

Patients who randomize to the standard of care arm will receive treatment for pulmonary MAC based on the approved ATS/IDSA guidelines. Changes to standard of care regimen may be made based on the investigator's discretion.

Azithromycin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in United States as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Approved in Canada as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

New York University

Collaborator

Trials

249

Recruited

229,000+

NTM Info & Research, Inc.

Collaborator

Trials

1

Recruited

50+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Azithromycin demonstrated effective in-vitro activity against Mycobacterium avium complex, with a minimum inhibitory concentration (MIC90) of 32 mg/L, suggesting its potential use in treating infections caused by this non-tuberculous mycobacterium.

The drug showed no effectiveness against Mycobacterium tuberculosis and Mycobacterium marinum, indicating that its therapeutic benefits may be limited to specific types of mycobacterial infections, particularly in patients with AIDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative activity of azithromycin against clinical isolates of mycobacteria. Watt, B., Rayner, A., Harris, G.[2019]

In a study using inbred C57BL/6 mice and a macrophage model, the combination of rifabutin, clarithromycin, and ethambutol showed the best results against the Mycobacterium avium strain 101, indicating that combination therapy may enhance efficacy.

However, for strain 2-151, the combination therapy did not significantly outperform clarithromycin alone, suggesting that the effectiveness of drug combinations can vary depending on the specific strain of bacteria being targeted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model. Furney, SK., Skinner, PS., Farrer, J., et al.[2021]

In a study involving congenitally athymic (nude) mice, the antibiotics rifapentine, azithromycin, and ethambutol were found to be highly effective against Mycobacterium kansasii when administered individually.

However, when these drugs were used in combination, they did not show increased effectiveness compared to their individual use, indicating that combining these therapies may not provide additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment alternatives for Mycobacterium kansasii. Graybill, JR., Bocanegra, R.[2019]

A 46-year-old male with a rare congenital lung disease developed Nontuberculous Mycobacteria (NTM) pulmonary disease, highlighting the risk for patients with structural lung issues.

After 16 months of treatment with a combination of antibiotics, including azithromycin and rifampin, the patient achieved culture conversion at 4 months and showed no recurrence of NTM disease for 6 months, indicating the efficacy of the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nontuberculous mycobacterial pulmonary disease in a patient with unilateral pulmonary artery agenesis: Case report. Yoon, CS., Park, HK., Lee, JK., et al.[2023]

In a study of 111 patients with pulmonary Mycobacterium avium complex (MAC) disease treated with clarithromycin, 75.7% had a good short-term response, and 82.0% achieved good long-term outcomes, indicating the treatment's overall efficacy.

Short-term treatment responses were particularly predictive of long-term outcomes for patients with large lesions, suggesting that monitoring early responses could help tailor longer treatment plans for better results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and outcomes of clarithromycin treatment for pulmonary MAC disease. Fujikane, T., Fujiuchi, S., Yamazaki, Y., et al.[2013]

In a 14-day clinical trial with 30 healthy volunteers, the combination of rifabutin with clarithromycin led to significantly increased levels of rifabutin and its active metabolite, raising concerns about potential drug interactions.

Severe neutropenia was observed in 14 participants receiving rifabutin, particularly in those also taking azithromycin or clarithromycin, highlighting the need for careful monitoring of blood cell counts in patients on rifabutin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. Apseloff, G., Foulds, G., LaBoy-Goral, L., et al.[2013]

In a trial involving 26 patients with pulmonary Mycobacterium avium complex (MAC) disease, high-dose rifabutin (600 mg/d) led to adverse events in 77% of participants, with 58% needing dosage adjustments or discontinuation due to side effects.

The most significant adverse effects included a substantial drop in white blood cell counts and gastrointestinal symptoms, prompting a recommendation to lower the rifabutin dose to 300 mg/d when used with macrolides for safer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Griffith, DE., Brown, BA., Girard, WM., et al.[2019]

In a study of 60 HIV-infected patients with Mycobacterium avium complex bacteremia, ethambutol was the only drug that significantly reduced mycobacteremia levels after 4 weeks of treatment, showing a median decrease of -0.60 log10 cfu/mL.

Clofazimine and rifampin did not demonstrate significant antibacterial activity against M. avium complex, with changes in colony counts being minimal, indicating that ethambutol should be prioritized in treatment regimens for this infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS. Kemper, CA., Havlir, D., Haghighat, D., et al.[2019]

In two cases of Mycobacterium avium-intracellulare complex (MAC) infections, one child with AIDS died despite treatment, highlighting the challenges in managing MAC in immunocompromised patients.

The second child, without immunodeficiency, successfully recovered from a MAC-related mass after a combination therapy including streptomycin, ethambutol, clofazimine, and rifabutin, demonstrating that aggressive multidrug therapy can be effective in non-immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nontuberculous mycobacterial infections in pediatric patients. Levin, RH., Bolinger, AM.[2013]

In a study of 119 patients with Mycobacterium avium complex lung disease, the two-drug regimen of clarithromycin and ethambutol resulted in a higher rate of sputum culture conversion (55.0%) compared to the three-drug regimen that included rifampicin (40.6%).

The incidence of adverse events leading to treatment discontinuation was higher in the three-drug group (37.2%) compared to the two-drug group (26.6%), suggesting that the simpler regimen may be safer and equally effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study. Miwa, S., Shirai, M., Toyoshima, M., et al.[2014]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31000680/

Outcomes of hypertonic saline inhalation as a treatment ... Outcomes of hypertonic saline inhalation as a treatment modality in nontuberculous mycobacterial pulmonary disease.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04921943

Study Details | NCT04921943 | Hypertonic Saline for MAC The MAC-HS study is a testing whether hypertonic saline helps improve symptoms and clearance of mycobacteria in patients with M. avium complex lung infections.

3. withpower.com withpower.com/trial/phase-4-mycobacterium-infections-4-2021-543b8

Hypertonic Saline for Nontuberculous Mycobacterial Lung ... This trial is testing whether inhaling a saltwater solution can help patients with a specific lung infection by making it easier to clear mucus from their ...

4. researchgate.net researchgate.net/publication/332520777_Outcomes_of_hypertonic_saline_inhalation_as_a_treatment_modality_in_nontuberculous_mycobacterial_pulmonary_disease

Outcomes of hypertonic saline inhalation as a treatment ... The study was initiated based on earlier in vitro findings suggesting that 5.8% HS could kill Mycobacterium avium complex (MAC) and inhibit Mycobacterium ...

5. trialstoday.org trialstoday.org/trial/NCT04921943

Hypertonic Saline for MAC The MAC-HS study is a testing whether hypertonic saline helps improve symptoms and clearance of mycobacteria in patients with M. avium complex ...

6. clinicaltrial.be clinicaltrial.be/en/details/34440?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Hypertonic Saline Inhalation for Mycobacterium Avium ... SALINE is an open-label, randomized, two-arm controlled study that investigates the effect of Hypertonic Saline inhalation (HSi) plus best ...