Intermittent versus Daily Therapy for Noncavitary Mycobacterium avium Complex Pulmonary Disease: An Open-label Randomized Trial.

Abstract

Rationale: Patients with noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex pulmonary disease (MAC-PD) are treated intermittently three times a week, although no randomized controlled trials have been conducted comparing three times weekly to daily therapy. Objectives: To assess the tolerability, safety, and efficacy of intermittent versus daily treatment in patients with previously untreated noncavitary NB MAC-PD Methods: In an open-label study, patients were randomly assigned to the intermittent therapy group receiving clarithromycin 1000 mg, rifampicin 600 mg, and ethambutol 25 mg/kg (maximum 1000 mg) three days a week, or the daily therapy group receiving clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 15 mg/kg (maximum 750 mg) daily for one year. The primary endpoint was the proportion of patients requiring modification of the initial treatment regimen. Results: Twenty-one Japanese hospitals participated in the study, enrolling 141 patients between May 2019 and December 2021. The full analysis set included 138 participants (intermittent therapy = 70; daily therapy = 68). There were no significant differences between the intermittent and daily therapy groups in terms of the regimen modification rate (20.0% (14/70) versus 33.8% (23/68); adjusted odds ratio 0.48, 95% confidence interval 0.22 to 1.05; p=0.06) or culture conversion (70.3% vs. 80.0%, p=0.53), time to culture conversion (28.0 vs. 28.5 days, p=0.89), improvement in chest CT findings (60.9% vs. 71.0%, p=0.30), or clarithromycin resistance development (1.4% vs. 0%, p=1.00). Elevated AST (16.9% vs. 41.2%, p=0.003) and ALT (18.3% vs. 44.1%, p=0.002) were more common in the daily treatment group, while elevated bilirubin (11.3% vs. 1.5%, p=0.04) and dysgeusia (14.1% vs. 1.5%, p=0.01) were more common in the intermittent treatment group. The daily treatment group exhibited a greater absolute change in the 36-Item Short Form Survey physical aspect score (-2.5 points) than the intermittent treatment group (2.1 points) (p=0.01). Conclusion: Intermittent treatment was not significantly better tolerated than daily treatment for noncavitary NB MAC-PD. However, further studies with larger numbers of patients are needed. Clinical trial registration available at: https://jrct.niph.go.jp/en-top. ID: jRCTs031190008.