Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou
Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou
This is a prospective, randomized, parallel, controlled study comparing the efficacy and
 outcomes in the retreatment of pulmonary Tuberculosis (TB) in Guangzhou in a group using
 pretreatment susceptibility tests in selection of chemotherapy regimens and that in another
 group without using pretreatment susceptibility test results. The investigators hypothesize
 that selecting drug treatment on the basis of known susceptibility tests would lead to
 improved outcome compared with empiric treatment.
The aims are:1) To evaluate the efficacy and outcomes in the retreatment of pulmonary TB in
 Guangzhou by the use of pretreatment susceptibility tests in selection of chemotherapy
 regimens & 2) To study the predictive factors of unfavourable outcomes in the retreatment of
 pulmonary TB in Guangzhou, where unfavourable outcomes include treatment failures and
 relapses.

 The patients will be randomized into either a) The DOTS strategy consisting of the following
 measures: political commitment, case detection through bacteriologic evaluation, standardized
 treatment with supervision and patient support, an effective drug supply system, and a
 reporting and recording system that allows assessment of treatment; or b) The DOTS-Plus
 strategy includes additional measures including continuous drug resistance surveillance,
 culture, drug susceptibility testing for TB patients, and tailoring of individual drug
 regimen through the use of first and second-line drugs.

 The Primary end point is the 18-month combined treatment failure/ relapse (unfavourable
 outcome) among rifampicin resistant group. Secondary endpoints include the 30-month combined
 treatment failure/ relapse (unfavourable outcome) among rifampicin resistant group, multidrug
 resistant tuberculosis (MDR-TB) cases and all retreatment cases; Sputum smear/conversion rate
 at 2m, 3m, 8m, 12m, 18m, and 24m; Drug resistance rates to various drugs in particular
 rifampicin, and rate of MDR-TB. The predictive factors of unfavourable treatment outcomes
 (including failure and relapse) will be analysed.

 The management of retreatment cases by DOTS alone is often problematic, especially when there
 is resistance to rifampicin, and treatment failure / relapse with further resistances might
 result. With implementation of the "DOTS-plus" strategy, Hong Kong (HK) has achieved a low
 MDR-TB prevalence of around 1%. This study will provide important data on the predictors of
 treatment failure/ relapse of retreatment cases and whether the DOTS-plus strategy can
 effectively reduce the failure/relapse rate and the prevalence rate of MDR-TB in Guangzhou.
 The project will provide useful data on the surveillance, epidemiology and public health
 control of TB with a regional (cross-border) significance.
Inclusion Criteria:

 All consecutive smear positive pulmonary TB patients aged at least 18 years, with past
 history of TB treatment, diagnosed with a new episode of active pulmonary TB requiring
 treatment will be recruited and randomized into two groups, with Group A with management
 based essentially on the DOTS strategy, while Group B based essentially on the DOTS-plus
 strategy.

 Exclusion Criteria:

 -  Age < 18 yrs;

 -  New TB cases (without past history of anti-TB treatment) will be excluded because they
 have a much lower risk for MDR-TB than the retreatment cases.