Use of an add-on dry powder inhaler (DPI) containing fixed doses of isoniazid, rifampicin, pyrazinamide, and levofloxacin did not increase sputum conversion in patients receiving standard oral therapy for pulmonary tuberculosis (TB); however, the combined antibiotic DPI did result in greater cough relief, according to study findings published in Pulmonary Pharmacology & Therapeutics.
The phase 2 study included 99 adult patients with newly diagnosed or previously treated pulmonary TB. Patients were randomized to receive either the add-on DPI containing anti-TB therapy (n=44) or a placebo DPI (n=47). In the add-on DPI group, patients received a capsule containing 5 mg isoniazid, 2 mg rifampicin, 16 mg pyrazinamide, and 2 mg levofloxacin. All patients received standard oral anti-TB therapy.
Researchers examined the Mycobacterium tuberculosis (MTB) sputum culture conversion rate over an 8-week treatment period. A similar proportion of patients in the study group and control arm demonstrated MTB sputum culture conversion at 2 months (77.3% vs 72.3%, respectively; relative risk [RR], 1.07; 95% CI, 0.84–1.36; P =.589). However, more patients who received the add-on intervention achieved conversion by week 4 (50.0% vs 31.9%).
Additionally, the study group had a significantly lower rate of cough by 4 weeks of treatment compared with the placebo group (52.3% vs 91.5%, respectively; RR, 0.57; 95% CI, 0.43–0.77; P <.001). Recovery from cough was also faster in patients who received the add-on DPI therapy. By 2 weeks of treatment, hemoptysis was reduced in 11.4% of patients in the study group and 23.0% of patients in the control group (P =.132).
There were no reports of dyspnea or severe adverse drug reactions. According to the investigators, the adverse events (AEs) associated with oral anti-TB therapies were considered “in normal ranges” in both groups. Common AEs observed equally in both groups included anorexia, dizziness, numbness, arthralgia, rash, and itching. In contrast, the active intervention arm had lower incidences of nausea (38.6% vs 74.5%; P =.001) and vomiting (43.2% vs 66.0%; P =.029).
Limitations of this study included its small sample size as well as the treatment of patients with pulmonary TB in the outpatient setting, which may limit the generalizability of the findings across larger, hospitalized patient groups.
Despite these limitations, the researchers suggest “the efficacy and safety outcomes from this phase 2 clinical trial showed that this new fixed-dose combination of four drugs in a DPI formulation could be promising for treatment” for patients with drug-susceptible pulmonary TB, given that the observed reduction in cough may represent an adequate treatment response and a potential subsequent “decreased risk of spread of infection.”
Disclosure: This clinical trial was supported by Government Pharmaceutical Organization. Please refer to the original article for a full list of disclosures.
Laohapojanart N, Ratanajamit C, Kawkitinarong K, Srichana T. Efficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis: A randomized controlled trial. Pulm Pharmacol Ther. Published online July 15, 2021. doi:10.1016/j.pupt.2021.102056