Hypertonic Saline for Nontuberculous Mycobacterial Lung Disease
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Oregon Health and Science University
Must not be taking: Bedaquiline, Macrolide, Ethambutol, Rifampin
Disqualifiers: HIV, Cystic fibrosis, Tuberculosis, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
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 lungs. Saltwater solutions have been used to improve mucus clearance in conditions like cystic fibrosis and chronic bronchitis.
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 data supports the effectiveness of the drugs used in the treatment for Nontuberculous Mycobacterial Lung Disease?
Is hypertonic saline safe for treating nontuberculous mycobacterial lung disease?
The safety of hypertonic saline specifically for nontuberculous mycobacterial lung disease isn't directly addressed in the provided studies. However, some antibiotics like rifabutin, when used in combination with others, have shown adverse effects such as severe neutropenia (low white blood cell count) and gastrointestinal symptoms, indicating the importance of monitoring for side effects during treatment.14567
What makes the drug combination of Azithromycin, Ethambutol, Hypertonic Saline, and Rifampin unique for treating nontuberculous mycobacterial lung disease?
This drug combination is unique because it includes hypertonic saline, which is not typically used in standard treatments for nontuberculous mycobacterial lung disease. Hypertonic saline may help clear mucus from the lungs, potentially enhancing the effectiveness of the antibiotics Azithromycin, Ethambutol, and Rifampin, which are known to be active against various mycobacterial infections.148910
Eligibility Criteria
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 am 18 years old or older.
See 3 more
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.
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- Azithromycin (Antibiotic)
- Ethambutol (Antibiotic)
- Hypertonic Saline (Other)
- Rifampin (Antibiotic)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Hypertonic salineExperimental Treatment1 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 CareActive Control3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Oregon Health & Science UniversityPortland, OR
University Health NetworkToronto, Canada
NYU Langone HealthNew York, NY
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Who Is Running the Clinical Trial?
Oregon Health and Science UniversityLead Sponsor
New York UniversityCollaborator
NTM Info & Research, Inc.Collaborator
University Health Network, TorontoCollaborator
References
Treatment alternatives for Mycobacterium kansasii. [2019]Mycobacterium kansasii was administered intravenously to congenitally athymic (nude) mice. Beginning 1 week later, rifapentine, azithromycin, ethambutol or combined therapy was initiated orally. All three drugs were highly active individually. Although there was no evidence of antagonism, combined therapy was not more effective than either component used alone.
Treatment of nontuberculous mycobacterial infections in pediatric patients. [2013]Two cases of Mycobacterium avium-intracellulare complex (MAC) infections are described, and the diagnosis, clinical features, and management of MAC infections are reviewed. In case 1, a four-year-old boy was diagnosed as having both acquired immunodeficiency syndrome (AIDS) and disseminated MAC infection. He was treated with a combination of isoniazid, ethambutol hydrochloride, rifabutin, and clofazimine. Results of susceptibility testing showed that the MAC was susceptible to rifabutin and ethambutol with intermediate susceptibility to isoniazid. The child developed severe adverse effects that necessitated the discontinuation of rifabutin therapy. Despite therapy, blood cultures remained positive for MAC. The child died of disseminated human immunodeficiency virus and MAC infection. In case 2, a 20-month-old girl was found to have a prevertebral retropharyngeal mass caused by MAC. The child did not have evidence of immunologic deficiency. She was treated with streptomycin, ethambutol, clofazimine, and rifabutin. Streptomycin was discontinued after three months. After seven months the mass decreased in size, allowing for surgical resection. Intraoperative cultures were negative for mycobacteria. Ethambutol, rifabutin, and clofazimine were continued for a total of 12 months, at which time the child was determined to be clinically and radiologically cured. Empiric multidrug antituberculous therapy should be initiated in patients with suspected disseminated nontuberculous mycobacterial infection because final isolation, identification, and susceptibility testing may take several weeks. Clofazimine and rifabutin, in combination with isoniazid and ethambutol, may be useful in the treatment of some MAC infections. At least four drugs are given, and regimens often consist of six drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study. [2014]Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen.
Activities of rifabutin, clarithromycin, and ethambutol against two virulent strains of Mycobacterium avium in a mouse model. [2021]Rifabutin, clarithromycin, and ethambutol, which were administered at concentrations similar to those used in clinical trials that are now under way, were tested for their capacities to inhibit the growth of two highly virulent isolates of Mycobacterium avium in inbred C57BL/6 mice and in vitro in a bone marrow-derived murine macrophage model. In the latter model rifabutin and clarithromycin had modest activities against strain 101 and somewhat better activities against strain 2-151. When they were tested in vivo, however, the best results, against strain 101 were seen when the three drugs were given in combination, whereas against strain 2-151 the combination therapy showed no significant improvement over that of clarithromycin given alone. It will be of interest to note to what degree the eventual outcomes of the current trials correlate with the predictions of these animal model systems.
The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS. [2019]The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined. Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks. Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia. The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046). In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4). Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M. avium infection.
Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. [2013]A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study was terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly. Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin. However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400% and 3,700%, respectively, of concentrations in those who received rifabutin alone. Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.
Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. [2019]We initiated a multidrug trial that included high-dose rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Twenty-six patients received rifabutin (600 mg/d) in combination with ethambutol, streptomycin, and either clarithromycin (500 mg b.i.d.; 15 patients) or azithromycin (600 mg/d; 11 patients). Rifabutin-related adverse events occurred in 77% of patients. Fifty-eight percent of patients required a dosage adjustment or discontinuance of rifabutin therapy. The most common adverse event was a reduction in the mean total white blood cell (WBC) count, which decreased from 8,600 +/- 2,800/mm3 before treatment to 4,500 +/- 2,100/mm3 during treatment (P = .0001). Although all patients had some decrease in WBC count, only three patients (12%) required a dosage adjustment for this reason. Other common adverse events included gastrointestinal symptoms (nausea, vomiting, or diarrhea; 42%) and abnormal liver enzyme levels (12%). Eight of 11 patients (73%) with gastrointestinal symptoms, including one patient with abnormal liver enzyme levels, required a rifabutin-dosage adjustment. The most severe adverse events, always requiring an adjustment of therapy, were a diffuse polyarthralgia syndrome (19%) and anterior uveitis (8%). The latter toxicity has previously been reported to occur only in patients with AIDS and was seen only in patients who also were receiving clarithromycin. On the basis of the current findings, we recommend that rifabutin be used at a dose of 300 mg/d in multidrug regimens that include a macrolide for treatment of MAC lung disease.
Comparative activity of azithromycin against clinical isolates of mycobacteria. [2019]Azithromycin exhibited in-vitro activity against 20 clinical isolates of Mycobacterium avium complex for which the MIC90 was 32 mg/L and 22 clinical isolates of other mycobacteria but showed no activity against 20 isolates of Mycobacterium tuberculosis (MIC90 > 128 mg/L) nor against the single isolate of Mycobacterium marinum tested (MIC 128 mg/L). These results suggest that the drug may prove useful for the prophylaxis and treatment of infections due to non-tuberculous mycobacteria, including M. avium complex in patients with AIDS.
Nontuberculous mycobacterial pulmonary disease in a patient with unilateral pulmonary artery agenesis: Case report. [2023]Nontuberculous mycobacteria (NTM) are ubiquitous organisms, but can cause a chronic pulmonary infection in some patients. Therefore, there could be host factors susceptible to this disease. A structural lung disease including damages of lungs caused by previous respiratory infection has been suggested as a host factor. Here we presented a case of NTM pulmonary disease which developed in a structural lung disease caused by a rare congenital lung disease. A 46-year-old male, was transferred to our hospital with an unexpandable lung after a closed thoracostomy due to spontaneous pneumothorax. His chest computed tomography showed an absence of left pulmonary artery at the time of admission. Mycobacterial culture in sputum, bronchial washing fluid, and pleural fluid showed the growth of NTM. Mycobacterium intracellulare was isolated from all positive cultures in the specimens. Combinations of drugs for M. intracellulare pulmonary disease including azithromycin, rifampin, and ethambutol were administered for 16 months. Amikacin intra venous treatment used for 6 months after treatment initiation. Culture conversion was achieved at 4 months of treatment. There was no evidence of recurrence of NTM pulmonary disease for 6 months after treatment. In conclusion, patients who have structural lung disease need to be careful monitoring about development of NTM pulmonary disease.
Efficacy and outcomes of clarithromycin treatment for pulmonary MAC disease. [2013]Retrospective review of patients with pulmonary Mycobacterium avium complex (MAC) disease treated with clarithromycin.