Skip to main content
OpenTrials
Completed

NCT Number: NCT03672630

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Mycobacterium Avium Complex Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections Mycobacterium Infections, Nontuberculous Mycobacterium avium-intracellulare Infection Nontuberculous Mycobacterium Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

University Health Network, Toronto, Ontario, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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

Treatment and study plan

Azithromycin

Drug

Azithromycin 500 MG Oral Tablet [ZITHROMAX]

Other names: Zithromax

Ethambutol

Drug

Ethambutol 25 mg/kg [MYAMBUTOL]

Other names: Myambutol

Rifampin

Drug

Rifampin 600 MG [RIFADIN]

Other names: Rifadin

Primary outcomes

  1. Acid-fast bacilli (AFB) culture negativity

    Time frame: 12 months post randomization

    Two consecutive negative AFB cultures by 12 months post randomization without reversion to positive

  2. Therapy completion

    Time frame: 12 months post randomization

    The proportion of patients who complete 12 months of therapy on their assigned regimen with "satisfactory adherence". "Satisfactory adherence" is defined as taking 80% of their prescribed doses/not missing more than 75 days of treatment.

Secondary outcomes

  1. QOL-B Respiratory Symptoms Score

    Time frame: 12 months post randomization

    Quality of Life-Bronchiectasis (QOL-B) with NTM module The QOL-B is a self-administered questionnaire that has been validated in patients with bronchiectasis. The questionnaire measures 8 separate domains: Physical Functioning, Role Functioning, Vitality, Emotional Functioning, Social Functioning, Treatment Burden, Health Perceptions, and Respiratory Symptoms.

  2. NTM Symptoms Score

    Time frame: 12 months post randomization

    Quality of Life-Bronchiectasis (QOL-B) with NTM module The QOL-B is a self-administered questionnaire that has been validated in patients with bronchiectasis. The NTM module includes 4 additional domains: Eating Problems, Body Image, Digestive Symptoms, and NTM Symptoms. No total score is calculated.

  3. PROMIS Fatigue 7a short form score

    Time frame: 12 months post randomization

    PROMIS Fatigue 7a short form score The PROMIS Fatigue item banks assess a range of self-reported symptoms over the past seven days, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. Each question has five response options ranging in value from one to five. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. The lowest possible raw score (indicating the highest subjective level of fatigue) is 7; and the highest possible raw score (indicating the lowest subjective level of fatigue) is 35.

  4. Fatigue AE proportion

    Time frame: Cumulative to 12 months

    Self-report, Moderate or worse

  5. Gastrointestinal AE proportion

    Time frame: up to 12 months

    Self-report, Moderate or worse: Nausea, diarrhea, decreased appetite, OR abdominal pain

  6. Liver AE proportion

    Time frame: up to 12 months

    Laboratory grade 2 or higher abnormality

  7. Macrolide resistance

    Time frame: 12 months post randomization

    Susceptibility at last positive culture

Sponsors and collaborators

Lead sponsor

Kevin Winthrop

Other

Collaborators

  • Columbia University
  • Emory University
  • James A. Haley Veterans Administration Hospital
  • Johns Hopkins University
  • Kaiser Permanente
  • Loma Linda University
  • Louisiana State University Health Sciences Center in New Orleans
  • Mayo Clinic
  • Medical University of South Carolina
  • National Jewish Health
  • New York University
  • Northwell Health
  • Patient-Centered Outcomes Research Institute
  • Stanford University
  • Temple University
  • The University of Texas Health Science Center at Tyler
  • University Health Network, Toronto
  • University of California, San Diego
  • University of California, San Francisco
  • University of Iowa
  • University of Kansas
  • University of Miami
  • University of North Carolina
  • University of Washington
  • University of Wisconsin, Madison
  • Vancouver Clinic

Registry information

Acronym: MAC2v3

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Sep 14, 2018
Registry last updated
Feb 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.