Antibiotic Therapy for Mycobacterium Avium Complex Infection

(MAC2v3 Trial)

Recruiting in Palo Alto (17 mi)

+25 other locations

Overseen by Kevin L Winthrop, MD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Waitlist Available

Sponsor: Kevin Winthrop

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Research Team

Kevin L Winthrop, MD, MPH

Principal Investigator

Oregon Health and Science University

Emily Henkle, PhD, MPH

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for adults over 18 who can consent and have a confirmed pulmonary Mycobacterium Avium Complex (MAC) infection. It's not for those with severe lung damage, planned lung surgery, extensive prior MAC treatment, cystic fibrosis, organ transplants, unmanageable drug interactions, or HIV.

Inclusion Criteria

I am over 18 years old.

I have a confirmed lung infection caused by MAC bacteria.

Ability to provide informed consent

Exclusion Criteria

I am allergic or cannot tolerate one of the medications in this study.

I have been diagnosed with HIV.

The study drug may interact with other medications you are taking in a way that could be harmful, and the doctor thinks it cannot be managed.

Treatment Details

Interventions

• Azithromycin (Macrolide Antibiotic)
• Ethambutol (Antimycobacterial Agent)
• Rifampin (Antimycobacterial Agent)

Trial Overview The study tests if two antibiotics (Azithromycin and Ethambutol) are as effective as three by adding Rifampin in treating pulmonary MAC disease. The goal is to see if fewer drugs reduce side effects without losing benefits during the usual 18-24 month treatment period.

Participant Groups

Group I: 2-drug regimen Active Control 2 Interventions

This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.

Group II: 3-drug regimen Active Control 3 Interventions

This arm is a 3 time per week (TIW) treatment regimen that includes azithromycin 500 mg po + ethambutol 25 mg/kg + rifampin 600 mg Treatment changes are at the discretion of the treating physician and patient. Where possible, changes in dosing or frequency that allow the patient to continue taking the assigned drugs during the 12 months study period are preferred.

Azithromycin is already approved in Canada for the following indications:

Approved in Canada as Azithromycin for:

• Respiratory tract infections
• Skin and soft tissue infections
• Sexually transmitted diseases
• Toxoplasmosis
• Malaria
• Preterm prelabor rupture of membranes

Who Is Running the Clinical Trial?

Kevin Winthrop

Lead Sponsor

Trials

4

Recruited

760+

Kaiser Permanente Hawaii

Collaborator

Trials

1

Recruited

470+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Dr. Afable

University of Iowa

Chief Medical Officer since 2005

MD from Loyola Stritch School of Medicine, MPH from the University of Illinois

Joel Harris

University of Iowa

Chief Executive Officer since 2023

B.A. in Economics from the University of Iowa, Post-baccalaureate Certificate in Narrative Communications from Northwestern University

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Michael O'Rand

University of North Carolina

Chief Executive Officer since 2022

PhD in Biology from Temple University

Dr. Miller

University of North Carolina

Chief Medical Officer since 2024

MD from Albert Einstein College of Medicine

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Dr. Katrina Armstrong

Columbia University

Chief Executive Officer

MD from Johns Hopkins University, MS in Epidemiology from Harvard School of Public Health

Dr. Katrina Armstrong

Columbia University

Chief Medical Officer

MD from Harvard Medical School

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Temple University

Collaborator

Trials

321

Recruited

89,100+

Dr. Kumar Budur

Temple University

Chief Medical Officer

MD, MS

Dr. Jeffrey M. Dayno

Temple University

Chief Executive Officer

MD from Temple University School of Medicine

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Dr. Christopher Longhurst

University of California, San Diego

Chief Medical Officer since 2021

MD and MS in Medical Informatics from UC Davis

Patty Maysent

University of California, San Diego

Chief Executive Officer since 2016

MBA from Stanford University

Loma Linda University

Collaborator

Trials

322

Recruited

267,000+

Adrian Cotton

Loma Linda University

Chief Medical Officer since 2020

MD

Richard H. Hart

Loma Linda University

Chief Executive Officer since 2015

MD, DrPH