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| ID | Type | Description | Link |
|---|---|---|---|
| K23AI159145-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| American College of Chest Physicians | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 14 Day Azithromycin Monotherapy | Experimental | For the first 14 days of therapy, participants will receive Azithromycin 250mg by mouth (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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug | Azithromycin 250 mg PO daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Mycobacterium Avium Colony Count in Sputum | 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 15. | Day 0 and Day 15 |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in the Mycobacterial Growth Indicator Tube (MGIT) | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 15. | Day 0 and Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Mycobacterium Avium Colony Count in Sputum | 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 8. | Day 0 and Day 8 |
| Mean Change in Mycobacterium Avium Colony Count in Sputum |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elisa H Ignatius, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17277290 | Background | 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. doi: 10.1164/rccm.200604-571ST. No abstract available. | |
| 27066084 |
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Of 10 consented participants, 10 met inclusion criteria and were assigned treatment.
Participants were recruited from the Johns Hopkins Center for Nontuberculous Mycobacteria and Bronchiectasis at Bayview Medical Center, Johns Hopkins Health System. Written informed consent was required for study participation.
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| ID | Title | Description |
|---|---|---|
| FG000 | 14 Day Azithromycin Monotherapy | For the first 14 days of therapy, participants will receive Azithromycin 250mg by mouth (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. Azithromycin: Azithromycin 250 mg PO daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 14 Day Azithromycin Monotherapy | For the first 14 days of therapy, participants will receive Azithromycin 250mg by mouth (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. Azithromycin: Azithromycin 250 mg PO daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change in Mycobacterium Avium Colony Count in Sputum | 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 15. | Posted | Mean | Standard Deviation | log10 CFU/mL | Day 0 and Day 15 |
|
Over the study period, at each visit, or if it is reported to the study team through hospitalization, for a total maximum duration up to 77 days.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 14 Day Azithromycin Monotherapy | For the first 14 days of therapy, participants will receive Azithromycin 250mg by mouth (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. Azithromycin: Azithromycin 250 mg PO daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chills | General disorders | DAERS 2.1 | Systematic Assessment |
The total sample size of N=10, while adequate for quantifying the early bactericidal activity (EBA), lacks the statistical power to perform subgroup analyses. Similarly, culture-based methods are inherently limited by their reliance on human capacity for sputum expectoration.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elisa Ignatius, MD, MSc | Johns Hopkins University School of Medicine | +1-410-955-1288 | eignati1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 7, 2025 | Apr 20, 2026 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 7, 2024 | Apr 20, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D015270 | Mycobacterium avium-intracellulare Infection |
| ID | Term |
|---|---|
| D009165 | Mycobacterium Infections, Nontuberculous |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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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 8 and day 15. |
| Day 8 to Day 15 |
| Mean Change in Mycobacterium Avium Colony Count in Sputum | 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. | Day 0 and 2 Months |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 8. | Day 0 and Day 8 |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between day 7 and day 14. | Day 7 and Day 14 |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and 2 months. | Baseline and 2 Months |
| Estimation of Plasma Azithromycin Area-under-the-curve (AUC) Following Oral Dosing Azithromycin | Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) |
| Estimation of Plasma Azithromycin Area-under-the-curve (AUC) Following Oral Dosing Azithromycin | Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. | 2 and 6 hours post-dose on day 29 (range: 25-31 days) |
| Estimation of Maximum Plasma Concentration (Cmax) of Azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) |
| Estimation of Maximum Plasma Concentration (Cmax) of Azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | 2 and 6 hours post-dose on day 29 (range: 25-31 days) |
| Background |
| 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. |
| 10671330 | Background | 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. doi: 10.1086/313644. |
| 28954780 | Background | 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):1602503. doi: 10.1183/13993003.02503-2016. Print 2017 Sep. |
| 30172726 | Background | 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. |
| 6774638 | Background | 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. doi: 10.1164/arrd.1980.121.6.939. No abstract available. |
| 22828481 | Background | 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. |
| 18762155 | Background | 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. |
| 26647433 | Background | 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. No abstract available. |
| 8173775 | Background | 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. doi: 10.1164/ajrccm.149.5.8173775. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Baseline Colony Forming Unit | Mean | Standard Deviation | log10 CFU/mL |
|
| Baseline Time to Positivity | Median | Full Range | hours |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | Mean Change in Time to Positivity of Mycobacterium Avium Growth in the Mycobacterial Growth Indicator Tube (MGIT) | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 15. | Posted | Mean | Standard Deviation | hours | Day 0 and Day 15 |
|
|
|
| Secondary | Mean Change in Mycobacterium Avium Colony Count in Sputum | 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 8. | Posted | Mean | Standard Deviation | log10 CFU/mL | Day 0 and Day 8 |
|
|
|
| Secondary | Mean Change in Mycobacterium Avium Colony Count in Sputum | 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 8 and day 15. | Posted | Mean | Standard Deviation | log10 CFU/mL | Day 8 to Day 15 |
|
|
|
| Secondary | Mean Change in Mycobacterium Avium Colony Count in Sputum | 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. | Posted | Mean | Standard Deviation | log10 CFU/mL | Day 0 and 2 Months |
|
|
|
| Secondary | Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 8. | Posted | Mean | Standard Deviation | hours | Day 0 and Day 8 |
|
|
|
| Secondary | Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between day 7 and day 14. | Posted | Mean | Standard Deviation | hours | Day 7 and Day 14 |
|
|
|
| Secondary | Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and 2 months. | Posted | Mean | Standard Deviation | hours | Baseline and 2 Months |
|
|
|
| Secondary | Estimation of Plasma Azithromycin Area-under-the-curve (AUC) Following Oral Dosing Azithromycin | Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. | Posted | Mean | Standard Deviation | μg/mL*h | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) |
|
|
|
| Secondary | Estimation of Plasma Azithromycin Area-under-the-curve (AUC) Following Oral Dosing Azithromycin | Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. | Posted | Mean | Standard Deviation | μg/mL*h | 2 and 6 hours post-dose on day 29 (range: 25-31 days) |
|
|
|
| Secondary | Estimation of Maximum Plasma Concentration (Cmax) of Azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | Posted | Mean | Standard Deviation | μg/mL | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) |
|
|
|
| Secondary | Estimation of Maximum Plasma Concentration (Cmax) of Azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | Posted | Median | Standard Deviation | μg/mL | 2 and 6 hours post-dose on day 29 (range: 25-31 days) |
|
|
|
| 1 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
| Fever | General disorders | DAERS 2.1 | Systematic Assessment |
|
| Calcium, low | General disorders | DAERS 2.1 | Systematic Assessment |
|
| Glucose, non-fasting, high | General disorders | DAERS 2.1 | Systematic Assessment |
|
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| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| Organic Chemicals |