NCT03672630

Comparison of Two- Versus Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 474 (actual)
• Sponsor: Kevin Winthrop · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Mycobacterium Avium Complex
• Nontuberculous Mycobacterium Infection

Interventions

Type	Name	Description
DRUG	Azithromycin	Azithromycin 500 MG Oral Tablet \[ZITHROMAX\]
DRUG	Ethambutol	Ethambutol 25 mg/kg \[MYAMBUTOL\]
DRUG	Rifampin	Rifampin 600 MG \[RIFADIN\]

Timeline

• Start date: 2019-02-22
• Primary completion: 2026-01-08
• Completion: 2026-01-08
• First posted: 2018-09-14
• Last updated: 2026-02-02

Locations

26 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study