Clinical trial NCT02758236: Tuberculosis Research of INA-RESPOND On Drug Resistance
Official title: Tuberculosis Research of INA-RESPOND On Drug Resistance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Tuberculosis
MDR TB
Lead sponsor: Ina-Respond
Sponsor class: OTHER
Collaborators: name: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2016-05-02
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Presumptive TB patients, \>=18 years old. This study will analyze 500 subjects bacteriologically confirmed TB (250 new cases and 250 previously treated cases). To obtain the numbers, we estimate to enroll 1357 subjects presumptive TB (1000 new cases and 357 previously treated cases). These numbers are made based on our estimation that 25% of presumptive new TB cases and 70% of presumptive previously treated TB cases will be bacteriologically confirmed.

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)

Eligibility criteria: 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).

Primary outcomes:
measure: Number of MDR TB Cases Amongst New TB Cases and Previously Treated TB Cases
timeFrame: 2 months after enrollment
Secondary outcomes:
measure: Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up
timeFrame: 12- 30 months
measure: Factors for Treatment Success.
timeFrame: 12-30 months
measure: Factors of Treatment Interruption.
timeFrame: 12-30 months
measure: TB Case Category
timeFrame: 12-30 months
measure: The Performance of AFB and Xpert MTB/RIF
timeFrame: 12-30 months
measure: The Performance of Xpert MTB/RIF
timeFrame: 12-30 months
Other outcomes:
Locations:
city: Denpasar
country: Indonesia
facility: Site 520: University of Udayana/Sanglah Hospital
state: Bali
city: Semarang
country: Indonesia
facility: Site 560: University of Diponegoro/ Dr. Kariadi Hospital
state: Central Of Java
city: Jakarta
country: Indonesia
facility: Site 590: Persahabatan Hospital
state: DKI Jakarta
city: Surabaya
country: Indonesia
facility: Site 570: University of Airlangga/ Dr. Soetomo Hospital
state: East Of Java
city: Medan
country: Indonesia
facility: Site 600 : Adam Malik Hospital
state: North Sumatra
city: Makassar
country: Indonesia
facility: Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
city: Yogyakarta
country: Indonesia
facility: Site 580: University of Gadjah Mada/ Dr. Sardjito Hospital
Study officials:
affiliation: Persahabatan Hospital, Jakarta
name: Dr. dr. Erlina Burhan, SpP(K), MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, Ochodo EA, Haraka F, Zwerling AA, Pai M, Steingart KR, Horne DJ. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2(2):CD009593. doi: 10.1002/14651858.CD009593.pub5.