The MAC2v3 Randomized Pragmatic Clinical Trial of Macrolide-based 2- Versus 3-drug Treatment for Mycobacterium Avium Complex Pulmonary Disease: Baseline Participant Characteristics

Abstract Background: Treatment for Mycobacterium avium complex pulmonary disease (MAC-PD) consists of multidrug macrolide-based regimens taken for 15+ months. Current guideline-based treatment recommendations were developed by expert consensus without rigorous testing. Here we report baseline characteristics of a large population initiating treatment for MAC-PD as part of the MAC2v3 pragmatic randomized trial. Methods: The MAC2v3 trial randomizes non-cavitary treatment-naïve patients with MAC-PD to azithromycin and ethambutol +/- rifampin thrice weekly, stratified by bronchoalveolar lavage (BAL) only or sputum +/- BAL cultures to meet American Thoracic Society/Infectious Disease Society of America MAC-PD criteria. Baseline data collection covered a 12-month lookback period and included demographics, smoking history, culture results, comorbidities, airway clearance use, smoking history, and patient-reported outcomes (e.g. QOL-Bronchiectasis [QOL-B], scaled 0-100 with 100=no symptoms). Results: The study closed to enrollment 10/25/2024; observation is ongoing with endpoints evaluated at 12 months. Baseline data entry was completed for all 471 randomized through 9/30/2024. Mean age was 69, 395 (80%) were female, and 376 (84%) were white race (Table). At baseline 390 (83%) had a bronchiectasis diagnosis and 65 (14%) had a diagnosis of chronic obstructive pulmonary disease. A total of 186 (40%) were acid fast bacillus (AFB) smear positive. Species included M. avium (n=224, 48%), M. avium-intracellulare complex (n=176, 38%), M. intracellulare (n=51, 11%), and M. chimaera (n=8, 2%). Overall, 431 (92%) had a chest CT scan and 326 (69%) had pulmonary function testing results. Mean FEV1 % predicted was 80.5% and FVC % predicted was 87.8%. QOL-B respiratory symptoms scores were mean 67.5 (SD 19.2), physical functioning was mean 59.2 (SD 32.4), and health perceptions was mean 46.1 (SD 23.3). Prior to initiating treatment, 136 (29%) had baseline audiology testing, 245 (52%) had an electrocardiogram, 157 (33%) had a visual acuity exam, and 99 (21%) had a color vision exam. We observed no major differences in characteristics across randomization strata. BAL-only diagnosed participants were more likely to have common comorbidities except bronchiectasis (73% vs. 86% of sputum +/- BAL diagnosed), and less likely to be AFB culture smear positive (46% vs. 55%). They were also less likely to use airway clearance devices (38% vs. 59%) or hypertonic saline (26% vs. 52%) but had similar pulmonary function testing results. Conclusion: Randomization achieved balance across treatment groups. We observed some differences between those diagnosed by BAL or sputum cultures suggestive of milder disease in the BAL group, supporting stratification in the study design.