for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
completion around
Principal Investigator
by Payam Nahid, MD, MPH
Headshot of Payam Nahid
Payam Nahid



NTM therapy consists of a multi-drug macrolide based regimen for 18-24 months. Treated patients frequently experience debilitating side effects, and many patients delay the start of antibiotic treatment due to these risks. Common side effects include nausea, diarrhea, and fatigue, and rare but serious toxicities include ocular toxicity, hearing loss, and hematologic toxicity. To date, most of the evidence underlying the current treatment recommendations has come from observational studies in which either a macrolide has been combined with rifampin and ethambutol, or in some cases combined with ethambutol alone. The proposed study will answer whether a third drug is necessary or whether taking two drugs can increase tolerability without a substantial loss of efficacy.


Mycobacterium avium complex (MAC) are a subset of nontuberculous mycobacteria (NTM), environmental bacteria that can cause chronic, debilitating pulmonary disease, primarily affecting those over age 60. The goals of treatment are to improve symptoms, stop disease progression, and clear the infection. We propose to address a longstanding controversy in the therapy of pulmonary MAC disease, whether patients must take three antibiotics concomitantly, or if two are sufficient. The study is a multicenter randomized pragmatic clinical trial to compare azithromycin + ethambutol (2-drug therapy) vs. azithromycin + ethambutol + rifampin (3-drug therapy) for non-cavitary pulmonary MAC disease. All clinical outcomes will be considered standard of care and abstracted from clinical records. Therapy changes and adverse events will be recorded at routine visits. Health-related quality of life (HRQoL) and self-reported toxicity will be captured centrally in a web-based database, and CT scans will be read centrally. Co-primary outcomes are culture conversion and tolerability of treatment. The primary analysis for culture conversion will be conducted as a per-protocol non-inferiority analysis, and the primary analysis for tolerability will be conducted as an intention-to-treat superiority analysis.


Mycobacterium Avium Complex, Nontuberculous Mycobacterium Infection, NTM, MAC, mycobacteria, nontuberculous mycobacteria, azithromycin, ethambutol, rifampin, Mycobacterium Infections, Mycobacterium avium-intracellulare Infection, Nontuberculous Mycobacterium Infections


You can join if…

Open to people ages 18 years and up

  • Culture positive pulmonary MAC meeting ATS/IDSA disease criteria
  • Age over 18 years
  • Ability to provide informed consent

You CAN'T join if...

  • Fibrocavitary disease
  • Planned surgery for MAC disease
  • Patients who have cumulatively taken 6 weeks or more of multi-drug antimicrobial treatment for MAC
  • Patients who are currently taking or have taken multi-drug antimicrobial treatment for NTM within the prior 30 days
  • Diagnosis of Cystic fibrosis
  • Diagnosis of HIV
  • History of solid organ or hematologic transplant
  • Significant drug-drug interaction not clinically manageable in the opinion of the investigator
  • Contraindication to any component of the study treatment regimen


  • UCSF accepting new patients
    San Francisco California 94110 United States
  • Stanford University accepting new patients
    Stanford California 94305 United States

Lead Scientist at UCSF

  • Payam Nahid, MD, MPH
    Dr. Nahid is Professor of Medicine, Director of Clinical Trials Operations in the UCSF Office of Research, Director of the UCSF CTSA Trials Innovation Network Hub, and Director of the UCSF Center for Tuberculosis. With over two decades of experience in global health research, he specializes in clinical trials and translational research focusing on TB and HIV/TB.


accepting new patients
Start Date
Completion Date
Kevin Winthrop
Phase 2/3 research study
Study Type
Expecting 500 study participants
Last Updated