Compared with 6 months of oral itraconazole treatment for chronic pulmonary aspergillosis, a 12-month course decreased the risk for recurrence at 2 years and increased the mean time to first recurrence. These findings were published in The Lancet Infectious Diseases.
Researchers conducted a single-center, open-label, randomized controlled trial at a chest clinic in India between July 2019 and August 2021 to determine the optimal duration of itraconazole for chronic pulmonary aspergillosis. Eligible patients included those who were naive to antifungals. Patients with active Mycobacterium tuberculosis or nontuberculous mycobacterial pulmonary disease and those with allergic, subacute, or invasive aspergillosis were excluded. Patients were randomly assigned to receive a 400-mg dose of oral itraconazole daily for either 6 or 12 months. The primary outcome was recurrence after 2 years.
Among patients who received itraconazole for 6 (n=81) and 12 months (n=83), the mean age was 44.3 years, 52% were men, and 86% had underlying tuberculosis infection.
After 2 years, 31 (38%) patients in the 6-month group and 8 (10%) in the 12-month group had recurrent chronic pulmonary aspergillosis (absolute risk reduction [aRR], 0.29; 95% CI, 0.16-0.40; P <.0001). Positive outcomes to itraconazole treatment were observed among 58 (72%) patients who received a 6-month course vs 73 (88%) who received a 12-month course (aRR, 0.16; 95% CI, 0.04-0.30). The mean time to first recurrence was 23 and 6 months for patients in the 12- and 6-month groups, respectively (P <.0001). Although 12 months of itraconazole was associated with a decreased risk for recurrence and increased time to first recurrence, the rate of all-cause mortality (n=16) was the same for both groups (10%).
Adverse events were reported by 10 (12%) patients in the 6-month treatment group vs 18 (22%) in the 12-month group, with nausea (both 50%) and anorexia nervosa (30% vs 20%) as the most common.
This study was limited by the use of different follow-up durations between the patient groups and the lack of blinding.
According to the researchers, “the results of this study warrant a revision of the current guidance for treating chronic pulmonary aspergillosis.”
Sehgal IS, Dhooria S, Muthu V, et al. Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India. Lancet Infect Dis. Published online April 13, 2022. doi:10.1016/S1473-3099(22)00057-3