Tuberculosis Research of INA-RESPOND On Drug Resistance

Completed

Conditions: MDR TB
Lung Tuberculosis

Registration Number: NCT02758236

Lead Sponsor: Ina-Respond

Brief Summary: This study is a prospective observational cohort study of TB patients who are treated or evaluated at 10 study sites. Patients presenting with cough for 2 weeks or longer with at least one additional TB symptom and a chest X-ray suggestive of TB, will be invited to be enrolled in the study. The signed informed consent will designate their willingness to participate on this study.

Detailed Description: This study is a prospective observational cohort study of TB patients who are treated or evaluated at 10 study sites. Patients presenting with cough for 2 weeks or longer with at least one additional TB symptom and a chest X-ray suggestive of TB, will be invited to be enrolled in the study. The signed informed consent will designate their willingness to participate on this study. Enrolled subjects will produce the sputum for bacteriological examination of M. tuberculosis by AFB, culture and Xpert. The sputum will also be tested by Xpert for drug resistance test. If the culture is positive, conventional DST will be performed, and M. tuberculosis isolates will be stored for spoligotyping and for future research on TB. All bacteriologicaly confirmed subjects will be followed for outcome assessment.

For all enrolled subjects chest X-ray results, demographic data, TB co-morbidities, symptoms, nutritional status, treatment regimens, compliance and outcome will be collected. In addition, sputum, blood and urine will also be collected for storage.

To estimate the proportion of MDR-TB amongst new and previously treated TB cases.

1. To evaluate accuracy of clinical diagnosis by comparing clinically defined TB to laboratory confirmed TB.

2. To compare AFB and Xpert MTB/RIF as TB diagnostic tests against culture result.

3. To estimate the sensitivity and specificity of Xpert MTB/RIF in detecting Rif susceptibility against DST.

4. To estimate the proportion of cured, completed, failed, died and lost to follow up as treatment outcomes on DS-TB and DR-TB cases

5. To evaluate the association of treatment success (cured or completed) with the following data:

1. Demographics (age, sex)

2. TB contact history

3. Smoking habit

4. Treatment seeking behavior

5. Co-morbidities (HIV, DM)

6. Primary and secondary drug resistance

7. Symptoms

8. Cavitary disease

9. Nutritional status

10. Treatment regimens

11. Patient reported compliance

12. Numbers of bacteria by AFB test

13. TB strains (e.g Beijing)

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 490

Inclusion Criteria

Patients suspected of having pulmonary TB
Cough ≥ 2 weeks
At least one other TB clinical symptom
- Fever
- Unexplained weight loss
- Loss of appetite
- Hemoptysis
- Shortness of breath
- Chest pain
- Night sweats
- Fatigue
Suggestive TB on chest x-ray based on pulmonologist or internist consultant of pulmonology opinion
Age ≥ 18 years' old
Willing to be treated or evaluated at study site
Willing to have specimens stored for use in future studies
Patient denies having TB treatment for more than 7 days in the last 1 month (30 days).

Exclusion Criteria

Pregnancy or any serious condition includes, but not limited to, liver disease, chronic kidney disease, and psychiatric illness that might interfere with study compliance (based on the clinician judgment).

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of MDR TB Cases Amongst New TB Cases and Previously Treated TB Cases	2 months after enrollment	AFB smear and GeneXpert were performed at the microbiology laboratory of the study site. Culture and drug susceptibility tests were conducted at appointed National TB Program Reference Laboratories.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up	12- 30 months	From 447 subjects with all sputum examination results, only 328 subjects confirmed by bacteriology and the treatment outcome were categorized as followed: 1. Cured 2. Failed 3. Died 4. Treatment completion 5. Lost to follow up
Factors for Treatment Success.	12-30 months	Protective factors were collected by interview with the subjects. 237 subjects with confirmed bacteriologically and cured or complete treatment were analyzed for this outcome.
TB Case Category	12-30 months	TB category was defined as clinically TB or bacteriologically confirmed TB. 447 subjects with sputum examination were analyzed for this outcome.
The Performance of Xpert MTB/RIF	12-30 months	Assess the performance of Rifampicin susceptibility results in Xpert MTB/RIF against result in drug susceptible test (DST) as gold standard. 312 subjects had positive sputum culture were used to assess the performance of Xpert MTB/RIF. 196 subjects were sensitive to Rif in Xpert MTB/RIF. While 116 subjects had resistant to Rif in Xpert MTB/RIF.
Factors of Treatment Interruption.	12-30 months	Risk factors of treatment interruption were collected by interview with the subject. 91 subjects were defined as lost to follow-up or treatment failure or died and analyzed for this outcome.
The Performance of AFB and Xpert MTB/RIF	12-30 months	Assess the sensitivity and specificity of AFB and Xpert MTB/RIF to culture as gold standard. 312 subjects had positive sputum culture were used for evaluation of sensitivity. Meanwhile, 99 subjects that had no bacterial evidence of MTB infection (AFB, culture, and Xpert negative) and 36 subjects that were only AFB and/or Xpert MTB/RIF positive were used to evaluate the specificity. In total 135 subjects were analyzed to evaluate the specificity.

Trial Locations

Locations (7): Site 520: University of Udayana/Sanglah Hospital
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Denpasar, Bali, Indonesia
Site 560: University of Diponegoro/ Dr. Kariadi Hospital
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Semarang, Central Of Java, Indonesia
Site 590: Persahabatan Hospital
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Jakarta, DKI Jakarta, Indonesia
Site 570: University of Airlangga/ Dr. Soetomo Hospital
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Surabaya, East Of Java, Indonesia
Site 600 : Adam Malik Hospital
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Medan, North Sumatra, Indonesia
Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
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Makassar, Indonesia
Site 580: University of Gadjah Mada/ Dr. Sardjito Hospital
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Yogyakarta, Indonesia