Lung Tuberculosis, MDR TB
Conditions
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)
Interventions
OTHERNo Intervention
No Intervention
Sponsors
National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
National Institute of Allergy and Infectious Diseases (NIAID)
Ina-Respond
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
Countries
Indonesia
Participant flow
Recruitment details
The recruitment period was from February 2017 through November 2018. The study was done at 7 hospitals in Indonesia.
Pre-assignment details
From total target 1357 subjects, only achieved 490 subjects enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Presumptive TB TB patients with cough for 2 weeks or longer with at least one additional TB symptom and a chest x-ray suggestive of TB. | 447 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Investigator discretion | 43 |
Baseline characteristics
| Characteristic | Presumptive TB |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 426 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 447 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 447 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 173 Participants |
| Sex: Female, Male Male | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 65 / 447 |
| other Total, other adverse events | 0 / 447 |
| serious Total, serious adverse events | 0 / 447 |
Outcome results
Primary
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.
Time frame: 2 months after enrollment
Population: TB cases with bacteriologically confirmed TB with positive MTB culture
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MDR TB Amongst New TB Cases | Number of MDR TB Cases Amongst New TB Cases and Previously Treated TB Cases | 23 Participants |
| MDR TB Amongst Previously Treated TB Cases | Number of MDR TB Cases Amongst New TB Cases and Previously Treated TB Cases | 64 Participants |
Secondary
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.
Time frame: 12-30 months
Population: Treatment success was defined as cured or complete treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MDR TB Amongst New TB Cases | Factors for Treatment Success. | Males | 143 Participants |
| MDR TB Amongst New TB Cases | Factors for Treatment Success. | Non-Smoking Group | 204 Participants |
| MDR TB Amongst New TB Cases | Factors for Treatment Success. | Normal/overweight (BMI>=18) | 125 Participants |
| MDR TB Amongst New TB Cases | Factors for Treatment Success. | New TB cases | 146 Participants |
| MDR TB Amongst New TB Cases | Factors for Treatment Success. | Lung lesion in CXR > 2 zones | 175 Participants |
Secondary
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.
Time frame: 12-30 months
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MDR TB Amongst New TB Cases | Factors of Treatment Interruption. | Previously treated | 54 Participants |
| MDR TB Amongst New TB Cases | Factors of Treatment Interruption. | Lung lesion in CXR >2 zones | 75 Participants |
| MDR TB Amongst New TB Cases | Factors of Treatment Interruption. | Male group | 56 Participants |
| MDR TB Amongst New TB Cases | Factors of Treatment Interruption. | Non-smoking group | 81 Participants |
| MDR TB Amongst New TB Cases | Factors of Treatment Interruption. | Underweight (BMI<18) | 51 Participants |
Secondary
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: 1. Cured 2. Failed 3. Died 4. Treatment completion 5. Lost to follow up
Time frame: 12- 30 months
Population: The proportion of treatment outcomes from all subjects with bacteriologically confirmed (n=328 subjects)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MDR TB Amongst New TB Cases | Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up | Cured | 222 Participants |
| MDR TB Amongst New TB Cases | Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up | Failed | 12 Participants |
| MDR TB Amongst New TB Cases | Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up | Died | 31 Participants |
| MDR TB Amongst New TB Cases | Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up | Treatment complete | 15 Participants |
| MDR TB Amongst New TB Cases | Number of Participants Who Were Cured, Failed, Died, Treatment Completion, and Lost to Follow-up | Treatment lost to follow-up | 48 Participants |
Secondary
TB Case Category
TB category was defined as clinically TB or bacteriologically confirmed TB. 447 subjects with sputum examination were analyzed for this outcome.
Time frame: 12-30 months
Population: TB category was defined as clinically TB or bacteriologically confirmed TB. 447 subjects with sputum examination were analyzed for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MDR TB Amongst New TB Cases | TB Case Category | 99 Participants |
| MDR TB Amongst Previously Treated TB Cases | TB Case Category | 348 Participants |
Secondary
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.
Time frame: 12-30 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MDR TB Amongst New TB Cases | The Performance of AFB and Xpert MTB/RIF | 269 Participants |
| MDR TB Amongst Previously Treated TB Cases | The Performance of AFB and Xpert MTB/RIF | 117 Participants |
| Sensitivity Xpert MTB/RIF | The Performance of AFB and Xpert MTB/RIF | 304 Participants |
| Specificity Xpert MTB/RIF | The Performance of AFB and Xpert MTB/RIF | 99 Participants |
Secondary
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.
Time frame: 12-30 months
Population: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MDR TB Amongst New TB Cases | The Performance of Xpert MTB/RIF | Xpert negative | 6 Participants |
| MDR TB Amongst New TB Cases | The Performance of Xpert MTB/RIF | Xpert sensitive | 165 Participants |
| MDR TB Amongst New TB Cases | The Performance of Xpert MTB/RIF | Xpert resistant | 25 Participants |
| MDR TB Amongst Previously Treated TB Cases | The Performance of Xpert MTB/RIF | Xpert negative | 2 Participants |
| MDR TB Amongst Previously Treated TB Cases | The Performance of Xpert MTB/RIF | Xpert sensitive | 2 Participants |
| MDR TB Amongst Previously Treated TB Cases | The Performance of Xpert MTB/RIF | Xpert resistant | 112 Participants |