Shortening short course chemotherapy: a randomised clinical trial for treatment of smear positive pulmonary tuberculosis with regimens using ofloxacin in the intensive phase.

Tuberculosis Research Centre

Indian Journal of Tuberculosis; 2002; 49; 27-38.          

Background : The recommended 6-month regimens for the treatment of pulmonary tuberculosis are highly effective in the setting of clinical trials, yet cumbersome to implement under practical conditions. Shorter treatment regimens would ease drug administration for both patients and providers; an effective, regimen of 3 or 4 months' duration would have significant practical advantages for tuberculosis control.

Methods : The study subjects were HIV negative adults with newly diagnosed, sputum smear and culture positive pulmonary tuberculosis. Eligible patients were randomly allocated to one of four regimens: (a) ofloxacin, isoniazid, rifampicin and pyrazinamide daily for 3 months; (b) regimen(a), followed by isoniazid and rifampicin twice a week for 1 month; (c) regimen(a), followed by isoniazid and rifampicin twice a week for 2 months; or (d) ofloxacin, isoniazid, rifampicin and pyrazinamide daily for 2 months, followed by isoniazid and rifampicin twice a week for 2 months. Each dose was administered under direct observation. The patients were assessed clinically and bacteriologically every month during and after treatment. Follow up will continue for 5 years; the results up to 24 months after treatment are presented here.

Results : A total of 529 patients were admitted to the study. Data for efficacy analysis are available for 416 patients; 113 were excluded primarily because of limited compliance. At the end of treatment, only 4 (1%) of 360 patients with initially drug-susceptible tuberculosis had an unfavorable bacteriological response (> 1 positive culture in the last 2 months of treatment), one patient in each regimen. Over a follow-up period of 2 years, 7 (8%) of 83, 3 (4%) of 81, 2 (2%) of 86, and 12 (13%) of 91 patients relapsed in regimens (a) through (d), respectively. Most (79%) of the relapses occurred in the 6 months following the cessation of treatment. Of the 47 patients with tuberculosis initially resistant only to isoniazid, 2 (4%) had an unfavorable bacteriological response at the end of treatment. However, bacteriological relapse occurred in 8 (19%) of 43 such patients who were assessed for relapse. Intention to treat analysis i.e., after including those who had inadequate therapy, of 469 patients (which had 53 patients who received inadequate chemotherapy), showed that only 4 (3%) of 120, 6 (5%) of 115, 5 (4%) of 118 and 3 (3%) of 116 patients in the 4 regimens had an unfavourable bacteriological response at the end of treatment. Adverse reactions attributable to the anti-tuberculosis medications were observed in 31% (regimen d) to 44% (regimen c) of the patients, but a majority of the reactions were mild and manageable with symptomatic measures. Only 5% of patients had a reaction that required modification of the regimen.

Conclusion : Regimens of 4 or 5 months' duration that contain Ofloxacin and other first-line anti-tuberculosis agents for at least three months, can achieve high cure rates and low 24-month relapse rates in newly diagnosed patients with smear positive pulmonary tuberculosis without causing significant adverse reactions. These results indicate that ofloxacin containing regimens of 4-5 months achieve >95% efficacy with no increased incidence of adverse reactions and minimal relapses, permitting shortening of short-course chemotherapy.

Key words : Tuberculosis, Chemotherapy of tuberculosis, Short course chemotherapy, Ofloxacin, Fluoroquinolones, Clinical trials.

Back to List of publications / Home