A Study of Standard Drugs for Mycobacterium Avium Complex

Mycobacterium Avium Complex Clinical Trial

Official title:

Early Bactericidal Activity of Standard Drugs Used to Treat Mycobacterium Avium Complex: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04287049
• Other study ID #: IRB00221119
• Status: Recruiting
• Phase: Phase 2
• Start date: February 24, 2020
• Est. completion date: May 1, 2025

Study information

• Verified date: March 2024
• Source: Johns Hopkins University
• Contact: Kaylee Martin
• Phone: (410) 614-2724
• Email: kmart147[@]jh.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Age =18 years
• Isolation of M. avium intracellulare complex from a respiratory specimen in the preceding 6 months
• Fulfill American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria for MAC lung disease
• Intention by the treating clinician to treat for MAC lung disease.
• Ability to produce a sputum sample of at least 10mL in a 16 hour period
• Signed informed consent by the subject

Exclusion Criteria:

• Prior treatment for pulmonary MAC within the past 6 months
• Pregnancy
• HIV with a cluster of differentiation 4 (CD4) <350
• History of solid organ or hematologic transplant
• Contraindication to azithromycin
• 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.

Related Conditions & MeSH terms

• Mycobacterium Avium Complex
• Mycobacterium avium-intracellulare Infection
• Mycobacterium Infections

Intervention

Drug:
• Azithromycin
Azithromycin 250 mg PO daily

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 14.	Baseline and Day 14
Primary	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 14.	Baseline and Day 14
Secondary	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 7.	Baseline and Day 7
Secondary	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 7 and day 14.	Day 7 to Day 14
Secondary	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.	Baseline and 2 Months
Secondary	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 7.	Baseline and Day 7
Secondary	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
Secondary	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
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.	Pre-dose, 2, 4 and 6 hours post-dose on day 15, and 2 and 6 hours post-dose on day 29
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.	Pre-dose, 2, 4 and 6 hours post-dose on day 15
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.	2 and 6 hours post-dose on day 29