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Multicenter randomized pragmatic clinical trial comparing two- versus three-antibiotic therapy for pulmonary mycobacterium avium complex disease
Investigator (PI): Winthrop, Kevin
Performing Organization (PO): (Current): Oregon Health and Science University, School of Medicine, Department of Medicine, Division of Infectious Diseases / (503) 494-7735
Supporting Agency (SA): Patient-Centered Outcomes Research Institute (PCORI)
Initial Year: 2018
Final Year: 2024
Record Source/Award ID: PCORI/PCS-2017C2-7764
Funding: Total Award Amount: $5,951,017
Award Type: Contract
Award Information: PCORI: More information and project results (when completed)
Abstract: PCORI has identified the need for large studies that look at real-life questions facing diverse patients, caregivers, and clinicians. In 2014, PCORI launched the Pragmatic Clinical Studies initiative to support large-scale comparative effectiveness studies focusing on everyday care for a wide range of patients. The Pragmatic Clinical Studies initiative funded this research project. This research project is in progress. PCORI will post the research findings on the PCORI website within 90 days after the results are final. What is the research about? Mycobacterium avium complex, or MAC, is a type of bacteria that exists in water, soil, and dust. Most people don't get sick from MAC bacteria. But older adults, people with immune systems that don't work well, and those with lung disease have an increased risk of MAC infections. MAC infections most commonly affect the lungs, and symptoms include shortness of breath, fever, and fatigue. Treatment involves taking multiple types of antibiotics for 18 to 24 months. These antibiotics can have side effects such as nausea and diarrhea. The infection's symptoms and treatment side effects can decrease patients' quality of life. In this study, the research team is comparing the effects of treating MAC infection with two versus three different antibiotics. The team wants to know whether treatment with two different antibiotics is as effective as and better tolerated than treatment with three. Who can this research help? Results may help patients and doctors when considering how to treat MAC lung infections. What is the research team doing? The research team is enrolling 500 adults with MAC lung infections at 26 U.S. and Canadian sites in the study and assigning them by chance to receive treatment with either two or three different antibiotics. All patients receive standard care from their doctors. The research team is reviewing health records and collecting clinical data for the first 12 months of treatment to see how many patients (1) no longer have an infection, (2) finish 12 months of treatment, and (3) develop resistance to the antibiotics. Five times during the study period, the research team is surveying patients about their symptoms, treatment side effects, and quality of life. The team is comparing outcomes between patients who take two antibiotics and those who take three. Patients, patient advocates, and clinicians are providing input on the design, outcomes, and recruitment for the study. Research methods. Design: The study design is a randomized controlled trial. Population: The study population is 500 adults ages 18 and older with pulmonary MAC disease. Interventions/comparators are a 2-drug regimen (azithromycin and ethambutol) and a 3-drug regimen (azithromycin, ethambutol, and rifampin). Outcomes: Outcomes are (a) primary: acid-fast bacilli culture negativity and therapy completion with satisfactory adherence (defined as taking 80% of prescribed doses or not missing more than 75 days of treatment taken three times per week); and (b) secondary: respiratory symptoms, quality of life, fatigue, gastrointestinal symptoms, liver function, and macrolide resistance. The timeframe is 1-year follow-up for primary outcomes.
Abstract Archived: Nontuberculous mycobacteria (NTM) are environmental pathogens that increasingly cause chronic and progressive disability in some who are infected. Mycobacterium avium complex (MAC) is the most common NTM lung infection, associated with 80,000 prevalent infections in the U.S. MAC lung disease disproportionately affects the elderly and women, and those with existing underlying lung diseases like emphysema or bronchiectasis. Both the disease and its multidrug treatment lasting 18-24 months can impact quality of life. In a prior Patient-Centered Outcomes Research Institute (PCORI) Engagement Award, our patient partners identified better, more tolerable therapy as a top research priority. As the development of new drugs is many years away, we propose to evaluate two common treatment regimens, since the guidelines suggest that treatment with two drugs may be similar (non-inferior) to three drugs with regards to treatment response and improve tolerability, measured by the proportion of patients who complete 12 months of assigned therapy. Eligible patients, who have not been treated for MAC lung infections previously, will be randomized to 2-drug vs. 3-drug therapy and followed by their doctors as standard of care. We will review charts and collect clinical data for 12 months. In addition, patients will fill out surveys electronically every 3 months. We will also measure whether two drugs results in improved patient-reported health-related quality of life, fewer side effects, and poses any increased risk of macrolide resistance. We hope to provide much-needed data on the tradeoffs of two common MAC lung disease treatment regimens and support an evidence-based decision-making process for patients and their doctors.

MeSH Terms:
  • Antibiotics /*therapeutic use
  • Data Collection
  • Decision Making
  • Drug Therapy, Combination
  • Evidence-Based Medicine
  • Guidelines as Topic
  • Humans
  • Multicenter Studies as Topic
  • Mycobacterium avium Complex
  • Mycobacterium avium intracellulare Infection /*drug therapy
  • Outcome Assessment, Health Care
  • Patient-Centered Care
  • Pragmatic Clinical Trials as Topic
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Tuberculosis, Pulmonary /*drug therapy
  • United States
Country: United States
State: Oregon
Zip Code: 97239
UI: 20192426
CTgovId: NCT03672630
Project Status: Ongoing
Record History: ('2020: Archived abstract to Abstract Archived 1 field and added new abstract. Alternate Title: Using two versus three antibiotics to treat MAC lung infections',)