Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Directly Observed Therapy (DOTS) plus; Directly Observed Therapy (DOTS)
Intervention type(s): Other; Other
Intervention description(s): The regimen used to treat MDR-TB comprises 5 to 6 drugs to which the organism is or likely to be susceptible for the initial 6 months, and then 3 to 4 drugs subsequently. In addition, TB cases with rifampicin resistance but not amounting to MDR-TB are also at risk of unfavourable treatment outcomes. The availability of pretreatment susceptibility test results will provide a guide in selection of drugs in treating such cases.; The DOTS strategy (current strategy) consists 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. The standard regimen for treatment of new cases of pulmonary TB consists of 6 months treatment, with 4 drugs in the initial phase including isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin, followed by two drugs in the continuation phase including isoniazid and rifampicin. In the treatment of previously treated cases, a standard regimen consisting of 8 months treatment will be used.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: DOTS plus; DOTS; multidrug resistant tuberculosis (MDR TB)