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A Study of Standard Drugs for Mycobacterium Avium Complex

Primary Purpose

Mycobacterium Avium Complex

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Azithromycin
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mycobacterium Avium Complex

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Johns Hopkins University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

14 Day Azithromycin Monotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
February 25, 2020
Last Updated
March 29, 2023
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT04287049
Brief Title
A Study of Standard Drugs for Mycobacterium Avium Complex
Official Title
Early Bactericidal Activity of Standard Drugs Used to Treat Mycobacterium Avium Complex: a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 24, 2020 (Actual)
Primary Completion Date
March 10, 2024 (Anticipated)
Study Completion Date
May 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mycobacterium Avium Complex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
14 Day Azithromycin Monotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Zithromax
Intervention Description
Azithromycin 250 mg PO daily
Primary Outcome Measure Information:
Title
Change in Mycobacterium avium colony count in sputum
Description
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.
Time Frame
Baseline and Day 14
Title
Change in time to positivity of Mycobacterium avium growth in the Mycobacterial Growth Indicator Tube (MGIT)
Description
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between Baseline and Day 14.
Time Frame
Baseline and Day 14
Secondary Outcome Measure Information:
Title
Change in Mycobacterium avium colony count in sputum
Description
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.
Time Frame
Baseline and Day 7
Title
Change in Mycobacterium avium colony count in sputum
Description
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.
Time Frame
Day 7 to Day 14
Title
Change in Mycobacterium avium colony count in sputum
Description
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.
Time Frame
Baseline and 2 Months
Title
Change in time to positivity of Mycobacterium avium growth in MGIT
Description
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 7.
Time Frame
Baseline and Day 7
Title
Change in time to positivity of Mycobacterium avium growth in MGIT
Description
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between day 7 and day 14.
Time Frame
Day 7 and Day 14
Title
Change in time to positivity of Mycobacterium avium growth in MGIT
Description
The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and 2 months.
Time Frame
Baseline and 2 Months
Title
Estimation of plasma azithromycin area-under-the-curve (AUC) following oral dosing azithromycin
Description
Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods.
Time Frame
Pre-dose, 2, 4 and 6 hours post-dose on day 15, and 2 and 6 hours post-dose on day 29
Title
Estimation of maximum plasma concentration (Cmax) of azithromycin
Description
Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin.
Time Frame
Pre-dose, 2, 4 and 6 hours post-dose on day 15
Title
Estimation of maximum plasma concentration (Cmax) of azithromycin
Description
Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin.
Time Frame
2 and 6 hours post-dose on day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Nguyen
Phone
(443) 287-6283
Email
j.nguyen@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly Dooley
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elisa H Ignatius, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Study Director
Facility Information:
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Nguyen, MS
Phone
443-287-6283
Email
j.nguyen@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Keira A Cohen, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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A Study of Standard Drugs for Mycobacterium Avium Complex

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