Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention |
|---|---|
|
Pulmonary Tuberculosis |
Other: Directly Observed Therapy (DOTS) plus Other: Directly Observed Therapy (DOTS) |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
- combined treatment failure/ relapse (unfavourable outcome) among rifampicin resistant group. [ Time Frame: 18-month ] [ Designated as safety issue: No ]
- combined treatment failure/ relapse (unfavourable outcome) among rifampicin resistant group, MDR-TB cases and all retreatment cases; [ Time Frame: 30-month ] [ Designated as safety issue: No ]Other endpoints: Sputum smear/culture 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.
| Estimated Enrollment: | 320 |
| Study Start Date: | March 2009 |
| Estimated Study Completion Date: | February 2014 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: DOTS strategy
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 (2HRZE/4HR or 2HRZS/4HR). In the treatment of previously treated cases, a standard regimen consisting of 8 months treatment will be used (2HRZES/1HRZE/5HRE).
|
Other: Directly Observed Therapy (DOTS)
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 (2HRZE/4HR or 2HRZS/4HR). In the treatment of previously treated cases, a standard regimen consisting of 8 months treatment will be used (2HRZES/1HRZE/5HRE).
|
|
Active Comparator: DOTS plus
The DOTS-Plus strategy (the strategy to be tested) 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 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.
|
Other: Directly Observed Therapy (DOTS) plus
The DOTS-Plus strategy (the strategy to be tested) 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 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.
|
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, 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, 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| Ages Eligible for Study: | 18 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: David S Hui, MD | 852-26323128 | dschui@cuhk.edu.hk |
| Contact: Chi-Chiu Leung, MBBS | cc_leung@dh.gov.hk |
| China, Guangdong | |
| Guangzhou Chest Hospital | Recruiting |
| Guangzhou, Guangdong, China | |
| Contact: David S Hui, MD 852-26323128 dschui@cuhk.edu.hk | |
| Contact: Chi-Chiu Leung, MBBS cc_leung@dh.gov.hk | |
| Principal Investigator: Shou-Yong Tan, MD | |
| Principal Investigator: | David S Hui, MD | Chinese University of Hong Kong |
More Information
No publications provided
| Responsible Party: | Prof David Shu Cheong Hui, Professor of Respiratory Medicine, Chinese University of Hong Kong |
| ClinicalTrials.gov Identifier: | NCT01618422 History of Changes |
| Other Study ID Numbers: | CRE-2008.286-T |
| Study First Received: | June 11, 2012 |
| Last Updated: | June 12, 2012 |
| Health Authority: | Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee |
Keywords provided by Chinese University of Hong Kong:
|
DOTS plus DOTS MDRTB |
Additional relevant MeSH terms:
|
Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections |
Bacterial Infections Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections |
ClinicalTrials.gov processed this record on May 23, 2013