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

Patients with noncavitary nodular bronchiectatic (NB) complex pulmonary disease (MAC-PD) are treated intermittently three times per week, although no randomized controlled trials have been conducted comparing three times weekly with daily therapy. To assess the tolerability, safety, and efficacy of intermittent versus daily treatment in patients with previously untreated noncavitary NB MAC-PD. In an open-label study, patients were randomly assigned to the intermittent therapy group receiving clarithromycin 1,000 mg, rifampicin 600 mg, and ethambutol 25 mg/kg (maximum 1,000 mg) three days per week or the daily therapy group receiving clarithromycin 800 mg, rifampicin 450 mg, and ethambutol 15 mg/kg (maximum 750 mg) daily for 1 year. The primary endpoint was the proportion of patients requiring modification of the initial treatment regimen. 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 of 70] vs. 33.8% [23 of 68]; adjusted odds ratio, 0.48; 95% confidence interval, 0.22 to 1.05;  = 0.06) or culture conversion (70.3% vs. 80.0%;  = 0.53), time to culture conversion (28.0 vs. 28.5 d;  = 0.89), improvement in chest CT findings (60.9% vs. 71.0%;  = 0.30), or clarithromycin resistance development (1.4% vs. 0%;  = 1.00). Elevated aspartate aminotransferase (16.9% vs. 41.2%;  = 0.003) and alanine aminotransferase (18.3% vs. 44.1%;  = 0.002) were more common in the daily treatment group, whereas elevated bilirubin (11.3% vs. 1.5%;  = 0.04) and dysgeusia (14.1% vs. 1.5%;  = 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 Health Survey physical aspect score (-2.5 points) than the intermittent treatment group (2.1 points) ( = 0.01). 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 registered with https://jrct.mhlw.go.jp/en-top (jRCTs031190008).