1. Tuberculosis Research of INA-RESPOND on Drug-resistant
(TRIPOD)
JS Luwansa, April 30th 2015

2. The burden of tuberculosis in 2013 (estimation)
Background (1)
The burden of tuberculosis in 2013 (estimation)
Globally
9.0 million new TB cases (13% TB-HIV)
1.5 million deaths ( TB-HIV)
480,000 new MDR-TB cases
210,000 deaths from MDR-TB
Indonesia
Prevalence: 680,000 cases
Incidence: 460,000 cases (rank 5th)
Mortality: 64,000 cases
Source: WHO Global Tuberculosis Report 2014

3. Proportion of MDR-TB cases in Indonesia
Background(2)
Proportion of MDR-TB cases in Indonesia
Papua, 2004
Central Java, 2006
Makassar, 2007
Of new TB cases 2%
1.8%
4.1%
Of previously treated TB cases -
17.1%
19.2%

4. Background (3) Our main goal
To provide valid data which are beneficial for the government to better prepare a national program in controlling this disease
TRIPOD is INA-RESPOND’s first TB study, focused on questions specific to improve diagnosis and treatment of TB in Indonesia
TRIPOD closely observe a large number of various TB patients from many centers prospectively

5. Study Objectives Primary Objective Secondary Objectives
To estimate the proportion of MDR TB of new
and previously treated cases
Secondary Objectives
To estimate the proportion of cured,
completed, failed, died and lost to follow up
and treatment outcomes in drug susceptible & drug resistant cases

6. Secondary Objectives (continued)
Study Objectives (2)
Secondary Objectives (continued)
To evaluate the association of treatment success (cured or completed) with the following data.
Demographics (age, sex)
TB contact history
Smoking habit
Treatment seeking behavior
Comorbidities (HIV, Diabetes
Mellitus)
Primary or secondary drug
resistance
Symptoms
Cavity in the lung
Nutritional status
Treatment regimens
Compliance
Number of bacteria by
AFB test
TB strains (e.g., Beijing)

7. Secondary Objectives (continued)
Study Objectives (3)
Secondary Objectives (continued)
Comparison of clinically defined TB against laboratory confirmed TB for accuracy of diagnosis.
Comparison between AFB and X-pert as TB diagnostic tests against culture result.
Estimation of Rif susceptibility result sensitivity and specificity in X-pert against Rif susceptibility result in DST.  

8. Study Sites Persahabatan Hospital (Jakarta)
Dr. Soetomo Hospital (Surabaya)
Dr. Hasan Sadikin Hospital (Bandung)
Dr. Kariadi Hospital (Semarang)
Sanglah Hospital (Bali)
Prof. Dr. Sulianti Saroso Hospital (Jakarta)
Dr. Sardjito Hospital (Yogyakarta)

9. Study Design
This study is a prospective observational cohort study of new and previously treated TB patients. Patients will be treated as per standard of care according to national TB treatment guidelines and each study site policy.

10. Follow study procedure
Screening
Enrollment
Unable to produce sputum
End of study
Sputum collected for AFB, Xpert, culture
AFB and/or Xpert pos
AFB and Xpert neg
Follow study procedure
Treated & wait for culture
Not treated
Culture pos
Culture neg
Study
Plan

11. Screening
Patients (with or without TB treatment history) who meet the following criteria:
Age ≥18 years old
Patients suspected of having pulmonary TB
Cough ≥ 2 weeks
At least 1 other TB clinical symptoms (fever, unexplained weight loss, loss of appetite, hemoptysis, shortness of breath, chest pain, night sweats, fatigue)
Suggestive pulmonary TB chest X-ray result`s
Denies having TB treatment in the last 2 months
Willing to be treated/evaluated at study site
Willing to have specimens stored
No other medical condition (e.g. hepatitis or chronic kidney disease) and/or severe psychiatric illness that might interfere with study compliance (based on the clinician judgement)

12. Sample Size Estimation
250 confirmed new TB
1000 presumptive new TB
357 presumptive previously treated TB
250 confirmed previously treated TB
5 MDR-TB
30 MDR-TB
35 MDR-TB
25% pos
70% pos
Enrollment 2%
12%

13. Study Estimation Enrollment 1,000 Produce sputum
1000 presumptive new TB
357 presumptive previously treated TB
357 Unable to produce sputum
424
DS-TB
35 MDR-TB
Enrollment
End of Study
500 Bacteriologically Confirmed TB 76
MDR-TB
Based on Xpert
Based on DST
1,357 Subjects
500 Clinically Confirmed TB

14. Study Duration Accrual/Enrollment period: 2 years
Follow Up period: up to 2 years
Drug susceptible TB patients: until end of treatment
MDR TB patients: until end of treatment / max 24 months
► ► ► Total study duration: up to 4 years

15. Specimen Collection M.tb Isolate from sputum Blood: Urine serum,
plasma,
buffy coat
Urine

16. Case Definition (WHO 2013) Bacteriologically confirmed TB case:
A subject in whom a biological specimen is positive by smear microscopy, culture or WHO-approved rapid diagnostic test i.e. Xpert MTB/RIF
Clinically diagnosed TB case:
A subject who does not fulfil the criteria for bacteriologically confirmed TB but has been diagnosed with active TB by a clinician

17. Case Definition (WHO 2013) continued
MDR TB case:
Positive TB case with Rif and INH resistant result on DST
Rif-resistant TB case:
A subject with TB that is resistant to Rif, with or without resistance to other anti-TB drugs

18. Case Definition (WHO 2013) continued
DST procedures
All previously treated TB cases will be directly tested for 1st & 2nd line DST
Presumptive new TB cases with Rif susceptibility will be tested for 1st line DST. If resistant, further test for 2nd line.
Presumptive new TB cases with Rif resistant will be directly tested for 1st & 2nd line DST.

19. Case Definition (WHO 2013) continued
Data in follow up visit:
TB symptoms.
Body weight.
Treatment compliance.
Sputum results.
Data in end of study visit:
+ Chest x-ray.

20. “Every breath counts
Stop TB NOW!”
Thank You
#supportTRIPOD