A Study of Standard Drugs for Mycobacterium Avium Complex
Study Details
Study Description
Brief Summary
To assess the early bactericidal activity of Azithromycin 250mg by mouth daily over the first 14 days of treatment for Mycobacterium avium complex (MAC) lung disease.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
This research is being done to better understand several important aspects of treatment of Mycobacterium avium complex (MAC) lung infections using an early bactericidal activity (EBA) study design. MAC is an environmental bacteria that can cause chronic lung infection. Early bactericidal activity is the amount of bacterial killing that occurs during the first few weeks of antibiotic treatment. By collecting information about the EBA of azithromycin for MAC, the investigators will quantify the efficacy of azithromycin against pulmonary MAC.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 14 Day Azithromycin Monotherapy For the first 14 days of therapy, participants will receive Azithromycin 250mg PO daily as monotherapy. Beyond day 14, all participants will receive guideline-based standard multi-drug therapy for Mycobacterium avium lung disease, as dictated by the physicians treating the participants. |
Drug: Azithromycin
Azithromycin 250 mg PO daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in Mycobacterium avium colony count in sputum [Baseline and Day 14]
The early bactericidal activity of azithromycin for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 colony forming unit (CFU) per mL) in sputum between baseline and day 14.
- Change in time to positivity of Mycobacterium avium growth in the Mycobacterial Growth Indicator Tube (MGIT) [Baseline and Day 14]
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between Baseline and Day 14.
Secondary Outcome Measures
- Change in Mycobacterium avium colony count in sputum [Baseline and Day 7]
The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between baseline and day 7.
- Change in Mycobacterium avium colony count in sputum [Day 7 to Day 14]
The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between day 7 and day 14.
- Change in Mycobacterium avium colony count in sputum [Baseline and 2 Months]
The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between baseline and 2 months.
- Change in time to positivity of Mycobacterium avium growth in MGIT [Baseline and Day 7]
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 7.
- Change in time to positivity of Mycobacterium avium growth in MGIT [Day 7 and Day 14]
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between day 7 and day 14.
- Change in time to positivity of Mycobacterium avium growth in MGIT [Baseline and 2 Months]
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and 2 months.
- Estimation of plasma azithromycin area-under-the-curve (AUC) following oral dosing azithromycin [Pre-dose, 2, 4 and 6 hours post-dose on day 15, and 2 and 6 hours post-dose on day 29]
Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods.
- Estimation of maximum plasma concentration (Cmax) of azithromycin [Pre-dose, 2, 4 and 6 hours post-dose on day 15]
Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin.
- Estimation of maximum plasma concentration (Cmax) of azithromycin [2 and 6 hours post-dose on day 29]
Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years
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Isolation of M. avium intracellulare complex from a respiratory specimen in the preceding 6 months
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Fulfill American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria for MAC lung disease
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Intention by the treating clinician to treat for MAC lung disease.
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Ability to produce a sputum sample of at least 10mL in a 16 hour period
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Signed informed consent by the subject
Exclusion Criteria:
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Prior treatment for pulmonary MAC within the past 6 months
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Pregnancy
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HIV with a cluster of differentiation 4 (CD4) <350
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History of solid organ or hematologic transplant
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Contraindication to azithromycin
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Has any other condition that, in the opinion of the PI, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Johns Hopkins University School of Medicine | Baltimore | Maryland | United States | 21205 |
Sponsors and Collaborators
- Johns Hopkins University
Investigators
- Principal Investigator: Kelly Dooley, Johns Hopkins University
- Study Director: Elisa H Ignatius, MD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
- Asakura T, Nakagawa T, Suzuki S, Namkoong H, Morimoto K, Ishii M, Kurashima A, Betsuyaku T, Ogawa K, Hasegawa N; Nontuberculous Mycobacteriosis Japan Research Consortium (NTM-JRC). Efficacy and safety of intermittent maintenance therapy after successful treatment of Mycobacterium avium complex lung disease. J Infect Chemother. 2019 Mar;25(3):218-221. doi: 10.1016/j.jiac.2018.07.021. Epub 2018 Aug 29.
- Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Winter H, Becker P, Mendel CM, Spigelman MK. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet. 2012 Sep 15;380(9846):986-93. doi: 10.1016/S0140-6736(12)61080-0. Epub 2012 Jul 23.
- Donald PR, Diacon AH. The early bactericidal activity of anti-tuberculosis drugs: a literature review. Tuberculosis (Edinb). 2008 Aug;88 Suppl 1:S75-83. doi: 10.1016/S1472-9792(08)70038-6. Review.
- Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. Review. Erratum in: Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text.
- Griffith DE, Brown BA, Cegielski P, Murphy DT, Wallace RJ Jr. Early results (at 6 months) with intermittent clarithromycin-including regimens for lung disease due to Mycobacterium avium complex. Clin Infect Dis. 2000 Feb;30(2):288-92.
- Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis. 1980 Jun;121(6):939-49.
- Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, Park HY, Jeon K, Huh HJ, Ki CS, Lee NY, Chung MJ, Lee KS, Shin SJ, Daley CL, Kim H, Kwon OJ. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J. 2017 Sep 27;50(3). pii: 1602503. doi: 10.1183/13993003.02503-2016. Print 2017 Sep.
- Ryu YJ, Koh WJ, Daley CL. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives. Tuberc Respir Dis (Seoul). 2016 Apr;79(2):74-84. doi: 10.4046/trd.2016.79.2.74. Epub 2016 Mar 31. Review.
- Slaats MH, Hoefsloot W, Magis-Escurra C, Boeree MJ, Wattenberg M, Kuipers S, van Ingen J. Regimens for nontuberculous mycobacterial lung disease lack early bactericidal activity. Eur Respir J. 2016 Mar;47(3):1000-2. doi: 10.1183/13993003.00925-2015. Epub 2015 Dec 2.
- Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT, Onyi GO, Steingrube VA, Mazurek GH. Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease. Am J Respir Crit Care Med. 1994 May;149(5):1335-41.
- IRB00221119