Tuberculosis Research of INA-RESPOND On Drug Resistance (TRIPOD)

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.

Study Overview

• Status: Completed
• Conditions: Lung Tuberculosis; MDR TB
• Intervention / Treatment: Other: No Intervention

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)

• Study Type: Observational
• Enrollment (Actual): 490

Contacts and Locations

Study Locations

• Indonesia
  • Makassar, Indonesia, 90245
    • Site 550: University of Hassanudin/ Dr. Wahidin Sudirohusodo Hospital
  • Yogyakarta, Indonesia, 55284
    • Site 580: University of Gadjah Mada/ Dr. Sardjito Hospital
  • Bali
    • Denpasar, Bali, Indonesia, 80114
      • Site 520: University of Udayana/Sanglah Hospital
  • Central Of Java
    • Semarang, Central Of Java, Indonesia, 50244
      • Site 560: University of Diponegoro/ Dr. Kariadi Hospital
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 14340
      • Site 590: Persahabatan Hospital
  • East Of Java
    • Surabaya, East Of Java, Indonesia, 60286
      • Site 570: University of Airlangga/ Dr. Soetomo Hospital
  • North Sumatra
    • Medan, North Sumatra, Indonesia, 20136
      • Site 600 : Adam Malik Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of MDR TB Cases Amongst New TB Cases and Previously Treated TB Cases	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.	2 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up	From 447 subjects with all sputum examination results, only 328 subjects confirmed by bacteriology and the treatment outcome were categorized as followed: Cured; Failed; Died; Treatment completion; Lost to follow up	12- 30 months
Factors for Treatment Success.	Protective factors were collected by interview with the subjects. 237 subjects with confirmed bacteriologically and cured or complete treatment were analyzed for this outcome.	12-30 months
Factors of Treatment Interruption.	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.	12-30 months
TB Case Category	TB category was defined as clinically TB or bacteriologically confirmed TB. 447 subjects with sputum examination were analyzed for this outcome.	12-30 months
The Performance of AFB and Xpert MTB/RIF	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.	12-30 months
The Performance of Xpert MTB/RIF	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.	12-30 months

Collaborators and Investigators

• Sponsor: Ina-Respond
• Collaborators: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia; The National Institute of Allergy and Infectious Diseases, United States
• Investigators: Principal Investigator: Dr. dr. Erlina Burhan, SpP(K), MSc, Persahabatan Hospital, Jakarta

Publications and helpful links

General Publications

• 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:CD009593. doi: 10.1002/14651858.CD009593.pub5.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2017
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): April 26, 2021

Study Registration Dates

• First Submitted: April 4, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimated): May 2, 2016

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: INA102; U1111-1263-2311 (Other Identifier: WHO UTN Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No