4‐month moxifloxacin containing regimens in the treatment of patients with sputum‐positive pulmonary tuberculosis in South India – a randomised clinical trial

Abstract

background Shortening tuberculosis (TB) treatment duration is a research priority. We tested the efficacy and safety of 3-and 4-month regimens containing moxifloxacin in a randomised clinical trial in pulmonary TB (PTB) patients in South India. methods New, sputum-positive, adult, HIV-negative, non-diabetic PTB patients were randomised to 3-or 4-month moxifloxacin regimens [moxifloxacin (M), isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E)] or to a control regimen (2H 3 R 3 Z 3 E 3 /4R 3 H 3 ) [C]. The 4 test regimens were 3R 7 H 7 Z 7 E 7 M 7 [M3], 2R 7 H 7 Z 7 E 7 M 7 /2R 7 H 7 M 7 [M4], 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 M 3 [M4-I] or 2R 7 H 7 Z 7 E 7 M 7 /2R 3 H 3 E 3 M 3 [M4-IE]. Treatment was directly observed. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The primary end point was TB recurrence post-treatment.results Of 1371 patients, randomised, modified intention-to-treat (ITT) analysis was done in 1329 and per-protocol (PP) analysis in 1223 patients. Regimen M3 was terminated due to high TB recurrence rates. 'Favourable' response at end of treatment was 96-100% in the moxifloxacin regimens and 93% in the control regimen. Among these, the TB recurrence occurred in 4.1% in the M4 regimen and in 4.5% in the control regimen and demonstrated equivalence within a 5% margin (95% CI À3.68, 4.55). Similar findings were observed in modified ITT analysis. The TB recurrence rates in the M4-I and M4-IE regimens did not show equivalence with the control regimen. Sixteen (1.4%) of 1087 patients in the moxifloxacin regimens required treatment modification.conclusion The 4-month daily moxifloxacin regimen [M4] was found to be equivalent and as safe as the 6-month thrice-weekly control regimen.keywords tuberculosis, chemotherapy of tuberculosis, short course chemotherapy, moxifloxacin, fluoroquinolones Sustainable Development Goals (SDGs): SDG 3 (good health and well-being), SDG 17 (partnerships for the goals)

Predictors of unfavorable responses to therapy in rifampicin-sensitive pulmonary tuberculosis using an integrated approach of radiological presentation and sputum mycobacterial burden

“…Treatment was fully supervised, and patients were meticulously followed up to 24 months post treatment. A brief summary of the findings of the two studies is provided in section 1.2 of the supplementary material and the complete description of trial participants is available in the main manuscript of these published trials [ 13 , 14 ]. CXRs, standard postero-anterior view, were taken in Akimbo’s position in the erect posture, available from baseline till end of treatment, from the per-protocol population of the two clinical trials were excavated from the radiology department, independently interpreted and subsequently collated with de-identified patient data derived from these trials, by independent statisticians (Details of regimens elaborated in e-Supplement, Section 1.1 and in Table 1 ).…”

Authors’ Response to ‘False equivalence of four month and six‐month ATT regimen: a case of comparing apples and oranges’

“…The change to the daily 6-month regimen was implemented in the RNTCP after study enrolment was completed. We have clearly and explicitly acknowledged this issue in our manuscript and have identified it as one of the limitations of the trial [1]. Also, having said that, a shorter 4-month regimen with all its inherent advantages with a high cure rate at end of treatment and a TB recurrence rate of less than 5% after 24 months of follow-up is a benchmark that most TB programme managers would accept, we believe.…”

Correlation Between CT Features of Active Tuberculosis and Residual Metabolic Activity on End-of-Treatment FDG PET/CT in Patients Treated for Pulmonary Tuberculosis

“…This long duration of treatment with multiple drugs has a cost implication and a risk of non-adherence predisposing to the development of drug resistance. In recent times, many trials have been done to guide the design of shorter treatment regimens for PTB (2)(3)(4)(5). A reliable biomarker of cure is a crucial tool for the determination of sterilizing cure of tuberculous disease.…”