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| Name | Class |
|---|---|
| Guangzhou Institute of Respiratory Disease | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Directly Observed Therapy (DOTS) | Sham Comparator | The DOTS strategy (current standard 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. |
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| Directly Observed Therapy (DOTS) plus | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Directly Observed Therapy (DOTS) plus | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. | Cure (Completed for 8 months or more of therapy and culture converted in the last month of treatment, and on at least one previous occasion; for multidrug resistant TB (MDR-TB) switched to definitive second line therapy per protocol in the DOTS-plus group, sustained culture conversion for at least 6 months after initiation of second line therapy and no evidence of culture reversion up to the scheduled follow-up point); Treatment failure: not culture converted at 5 months or later; Defaulted: having interrupted treatment for 2 consecutive months or more; Transfer out: having been transferred to another recording and reporting unit and for whom the treatment outcome is not known; Death: a patient who died for any reason during the course of treatment Diagnosis revised: diagnosis revised to non-tuberculous mycobacterial infection or colonisation. Withdrawal: physician-initiated withdrawal for adverse effects, protocol violation or patient's decision to withdraw. | 18-month |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| David S Hui, MD | Chinese University of Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangzhou Chest Hospital | Guangzhou | Guangdong | China |
Altogether 391 patients were assessed and after excluding those who did not meet inclusion criteria or refused to participate in the study, 225 patients were successfully randomized into DOTS (n=114) and DOTS plus (n=111).
All consecutive patients suffering from tuberculosis (TB) of aged 18 years or older with past history of TB treatment of at least 1 month within 5 years and diagnosed with a new episode of sputum smear-positive pulmonary TB requiring treatment were recruited after informed consent.
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| ID | Title | Description |
|---|---|---|
| FG000 | DOTS Strategy | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Directly Observed Therapy (DOTS) | Other | 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. |
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| FG001 | 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. 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 |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | DOTS Strategy | 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. |
| BG001 | DOTS Plus | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| X ray lesions severity | Severity of chest x-ray (CXR) lesions is graded as follows: Mild: total area of involvement involving less than the size of right upper lobe; Moderate: total area of involvement was less than the size of right lung field but equal or bigger than right upper lobe; Severe: total area of involvement was bigger than right lung field. | Number | participants |
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| X ray showing cavitation | Number | participants |
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| Sputum tuberculosis culture | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. | Cure (Completed for 8 months or more of therapy and culture converted in the last month of treatment, and on at least one previous occasion; for multidrug resistant TB (MDR-TB) switched to definitive second line therapy per protocol in the DOTS-plus group, sustained culture conversion for at least 6 months after initiation of second line therapy and no evidence of culture reversion up to the scheduled follow-up point); Treatment failure: not culture converted at 5 months or later; Defaulted: having interrupted treatment for 2 consecutive months or more; Transfer out: having been transferred to another recording and reporting unit and for whom the treatment outcome is not known; Death: a patient who died for any reason during the course of treatment Diagnosis revised: diagnosis revised to non-tuberculous mycobacterial infection or colonisation. Withdrawal: physician-initiated withdrawal for adverse effects, protocol violation or patient's decision to withdraw. | Posted | Number | participants | 18-month |
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18 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 2 | 114 | 0 | 114 | ||
| EG001 | DOTS Plus | 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. | 2 | 111 | 0 | 111 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof David SC Hui | Chinese University of Hong Kong | 2632 3134 | dschui@cuhk.edu.hk |
| ID | Term |
|---|---|
| D014397 | Tuberculosis, Pulmonary |
| D018088 | Tuberculosis, Multidrug-Resistant |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| Male |
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| Moderate |
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| Severe |
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| Negative |
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| Culture grew Mycobacterium tuberculosis complex |
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| Culture grew non-tuberculosis mycobacterium |
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| Number of participants with treatment completion |
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| Number of participants defaulted follow up visit |
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| Number of participants who were transferred out |
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| Number of participants who were still on treatment |
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| Number of death |
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| Number of participants with diagnosis revised |
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| Number of participants who withdrew from the study |
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