Trial Outcomes & Findings for Directly Observed Therapy Short Course-Plus Versus DOTS for Retreatment of Relapsed Pulmonary Tuberculosis in Guangzhou (NCT NCT01618422)

Last Updated: 2015-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

225 participants

Primary outcome timeframe

18-month

Results posted on

2015-12-07

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	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.	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
Overall Study STARTED	114	111
Overall Study COMPLETED	114	111
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DOTS Strategy n=114 Participants 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.	DOTS Plus n=111 Participants 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.	Total n=225 Participants Total of all reporting groups
Age, Continuous	47.25 years STANDARD_DEVIATION 14.5 • n=5 Participants	48.83 years STANDARD_DEVIATION 17.07 • n=7 Participants	48.05 years STANDARD_DEVIATION 15.04 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	84 Participants n=7 Participants	170 Participants n=5 Participants
X ray lesions severity Mild	34 participants n=5 Participants	18 participants n=7 Participants	52 participants n=5 Participants
X ray lesions severity Moderate	45 participants n=5 Participants	47 participants n=7 Participants	92 participants n=5 Participants
X ray lesions severity Severe	35 participants n=5 Participants	46 participants n=7 Participants	81 participants n=5 Participants
X ray showing cavitation Positive	54 participants n=5 Participants	59 participants n=7 Participants	113 participants n=5 Participants
X ray showing cavitation Negative	60 participants n=5 Participants	52 participants n=7 Participants	112 participants n=5 Participants
Sputum tuberculosis culture not available	23 participants n=5 Participants	21 participants n=7 Participants	44 participants n=5 Participants
Sputum tuberculosis culture Culture grew Mycobacterium tuberculosis complex	79 participants n=5 Participants	77 participants n=7 Participants	156 participants n=5 Participants
Sputum tuberculosis culture Culture grew non-tuberculosis mycobacterium	12 participants n=5 Participants	13 participants n=7 Participants	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 18-month

Outcome measures

Outcome measures
Measure	DOTS Strategy n=114 Participants 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.	DOTS Plus n=111 Participants 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.
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants with treatment failure	12 participants	8 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants with cure	67 participants	73 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants with treatment completion	0 participants	0 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants defaulted follow up visit	0 participants	2 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants who were transferred out	12 participants	10 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants who were still on treatment	2 participants	0 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of death	2 participants	2 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants with diagnosis revised	12 participants	13 participants
Number of Participants Suffering From Treatment Failure/ Relapse (Unfavourable Outcome) Among Rifampicin Resistant Group. Number of participants who withdrew from the study	7 participants	3 participants

Adverse Events

DOTS Strategy

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

DOTS Plus

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DOTS Strategy n=114 participants at risk 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).	DOTS Plus n=111 participants at risk 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.
Infections and infestations Death	1.8% 2/114 • Number of events 2 • 18 months	1.8% 2/111 • Number of events 2 • 18 months

Other adverse events

Adverse event data not reported

Additional Information

Prof David SC Hui

Chinese University of Hong Kong

Phone: 2632 3134

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place