Clinical trial NCT01618422: Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou
Official title: A Randomized, Parallel, Controlled Study to Evaluate the Role of Directly Observed Therapy Short Course-Plus (DOTS-Plus) Versus DOTS for Retreatment of Relapsed Pulmonary TB in Guangzhou.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Tuberculosis
Keywords: DOTS plus
DOTS
multidrug resistant tuberculosis (MDR TB)
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Guangzhou Institute of Respiratory Disease
First posted: 2012-06-13
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group.
timeFrame: 18-month
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou Chest Hospital
state: Guangdong
Study officials:
affiliation: Chinese University of Hong Kong
name: David S Hui, MD
role: PRINCIPAL_INVESTIGATOR
References: