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

摘要

the setting of clinical trials, yet cumbersome to implement under practical conditions. Shorter treatment regimens wouldudease drug administration for both patients and providers: an effective. regimen of 3 or 4 months’ duration would haveudsignificant practical advantages for tuberculosis control.udMethods: The study subjects were HIV negative adults with newly diagnosed. sputum smear and culture positive pulmonaryudtuberculosis. Eligible patients were randomly allocated to one of four regimens: (a) Ofloxacin. Isoniazid. Rifampicin. andudPyrazinamide daily for 3 months; (b) regimen(a). followed by Isoniazid and Rifampicin twice a week for 1 month: (c)udregimen(a). followed by Isoniazid and Rifampicin twice a week for 2 months: or (d) Ofloxacin. Isoniazid. Rifampicin, andudPyrazinamide daily for 2 months, followed by Isoniazid and Rifampicin twice a week for 2 months. Each dose wasudadministered under direct observation. The patients were assessed clinically and bacteriologically every month during andudafter treatment. Follow up will continue for 5 years; the results up to 24 months after treatment are presented here.udResults :A total of 529 patients were admitted to the study. Data for efficacy analysis are available for 416 patients: 113udwere excluded primarily because of limited compliance. At the end of treatment, only 4 (1%) of 360 patients with initiallyuddrug-susceptible tuberculosis had an unfavourable bacteriological response (> 1 positive culture in the last 2 months ofudtreatment). 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.udand 12 (13%) of 91 patients relapsed in regimens (a) through (d), respectively. Most (79%) of the relapses occurred in theud6 months following the cessation of treatment. Of the 47 patients with tuberculosis initially resistant only to Isoniazid.ud2 (4%) had an unfavourable bacteriological response at the end of treatment. However, bacteriological relapse occurred inud8 (19%) of 43 such patients who were assessed for relapse. Intention to treat analysis i.e. after including those who hadudinadequate therapy. of 469 patients (which had 53 patients who received inadequate chemotherapy). showed that only 4ud(3%) of 120. 6 (5%) of 115, 5 (4%) of 118 and 3 (3%) of I16 patients in the 4 regimens had an unfavourableudbacteriological response at the end of treatment. Adverse reactions attributable to the anti-tuberculosis medications wereudobserved in 3 1% (regimen d) to 44% (regimen c) of the patients. but a majority of the reactions were mild and manageableudwith symptomatic measures. Only 5% of patients had a reaction that required modification of the regimen.udCorrclusions: Regimens of 4 or 5 months’ duration that contain Ofloxacin and other first-line anti-tuberculosis agents forudat least three months can achieve high cure rates and low 24-month relapse rates in newly diagnosed patients with smearudpositive pulmonary tuberculosis without causing significant adverse reactions. These results indicate that Ofloxacinudcontaining regimens of 4-5 months achieve >95% efficacy with no increased incidence of adverse reactions and minimaludrelapses. permitting shortening of short-course chemotherapy.