Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou

This study has been completed.
Sponsor:
Collaborator:
Guangzhou Institute of Respiratory Disease
Information provided by (Responsible Party):
Prof David Shu Cheong Hui, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01618422
First received: June 11, 2012
Last updated: November 3, 2015
Last verified: November 2015
  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.

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. [ Time Frame: 18-month ] [ Designated as safety issue: No ]

    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.



Enrollment: 225
Study Start Date: March 2009
Study Completion Date: February 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Directly Observed Therapy (DOTS)
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.
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. In the treatment of previously treated cases, a standard regimen consisting of 8 months treatment will be used.
Active Comparator: 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.
Other: Directly Observed Therapy (DOTS) plus
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, 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

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01618422

Locations
China, Guangdong
Guangzhou Chest Hospital
Guangzhou, Guangdong, China
Sponsors and Collaborators
Chinese University of Hong Kong
Guangzhou Institute of Respiratory Disease
Investigators
Principal Investigator: David S Hui, MD Chinese University of Hong Kong
  More Information

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
Results First Received: September 1, 2015
Last Updated: November 3, 2015
Health Authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee

Keywords provided by Chinese University of Hong Kong:
DOTS plus
DOTS
multidrug resistant tuberculosis (MDR TB)

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Lung Diseases
Mycobacterium Infections
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on May 24, 2016