Summary

for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
estimated completion:

Description

Summary

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.

Details

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.

Keywords

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

Eligibility

You can join if…

Open to people ages 18 years and up

  • Culture positive pulmonary MAC meeting ATS/IDSA disease criteria
  • Nodular-bronchiectatic findings on CT scan
  • Age over 18 years
  • Ability to provide informed consent

You CAN'T join if...

  • Fibrocavitary disease
  • Planned surgery for MAC disease
  • Prior multi-drug therapy for pulmonary NTM
  • Cystic fibrosis
  • 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

Locations

  • University of California, San Diego not yet accepting patients
    San Diego California 92103 United States
  • Standford University not yet accepting patients
    Stanford California 94305 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Kevin Winthrop
ID
NCT03672630
Phase
Phase 2/3
Study Type
Interventional
Last Updated