History of Changes for Study: NCT02457208
PK Study of Anti-TB Drugs
Latest version (submitted October 1, 2018) on
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Study Record Versions
Version A B Submitted Date Changes
1 May 26, 2015 None (earliest Version on record)
2 May 10, 2016 Recruitment Status, Study Status and Contacts/Locations
3 October 9, 2017 Study Status
4 October 1, 2018 Recruitment Status, Study Status, Contacts/Locations and Study Design
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Study NCT02457208
Submitted Date:  May 26, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: SMRU1407
Brief Title: PK Study of Anti-TB Drugs
Official Title: Studying the Blood Levels of First-line Anti-tuberculosis Drugs in Relation to Treatment Outcomes Among Newly Diagnosed Adults With Pulmonary Tuberculosis on the Thai-Myanmar Border
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2015
Overall Status: Not yet recruiting
Study Start: June 2015
Primary Completion: June 2016 [Anticipated]
Study Completion: June 2016 [Anticipated]
First Submitted: April 22, 2015
First Submitted that
Met QC Criteria:
May 26, 2015
First Posted: May 29, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
May 26, 2015
Last Update Posted: May 29, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: University of Oxford
Responsible Party: Sponsor
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This is a prospective descriptive and pharmacokinetic study will be conducted among newly diagnosed patients registered in the two SMRU TB clinics located on the Thai-Myanmar border. This study aims to recruit (1) 30 adults with HIV co-infection and (2) 30 adults without HIV co-infection in one year. Patients will be given the standard 6 month anti-TB drugs as per WHO guidelines.
Detailed Description:

The threat of tuberculosis and HIV remains as major public health issues all over the world. Multi-drug resistant tuberculosis (MDR TB) is also a rising public health issue. Currently available standardized TB treatment is 6 months in duration. Previous pharmacokinetic and pharmacodynamic (PK/PD) studies of anti-TB drugs have shown that a number of factors such as HIV status, diabetes, malnutrition, age, sex, race, genetics (e.g. NAT2 polymorphisms), drug- drug interactions and food interactions may cause variation of the PK and/or the treatment outcome. But the findings are not persistent from one study to another, for example Chideya S. et al's study in Botswana showed that lower Cmax of anti-TB drugs frequently occurred in TB/HIV coinfected patients and low Cmax of pyrazinamide was related to poor treatment outcomes. On the other hand Requena-Méndez A. et al's study showed the variation of rifampin Cmax was not related to HIV. Large between-patient variability in PK parameters was recently shown to be strongly associated with TB treatment failures and possibly the emergence of drug resistant TB.

The primary objective of this study aims to describe the plasma drug levels of the first-line anti- tuberculosis drugs in two different pulmonary TB patient groups: (1) adults with HIV co-infection and (2) adults without HIV co-infection. The secondary objectives are to investigate the clinical, microbiological and immunological outcomes of the study participants in relation to the plasma drug level and to conduct full genome sequencing and spoligotyping of MTB strains.

Plasma drug levels from venous blood will be measured densely 13 times per day at two occasions: after the first dose on Day 1 and 6 weeks after treatment. Thereafter plasma drug levels will be measured at six hours post-dose on months 2, 3, 4, 5 and 6.

Clinical, microbiological and immunological parameters such as liver and renal function, CRP and LTA4G and sputum examination (smear microscopy, RNA PCR, culture) to monitor clinical progress will also be measured.

The analysis on the plasma drug level in relation to the clinical and microbiological outcomes will be carried out in order to describe the PK/PD of anti-TB drugs and clinical, microbiogical and immunological outcomes in consideration of any possible factors that would influence the relationship between them.

Open or close this module Conditions
Conditions: Tuberculosis
Keywords: pharmacokinetics
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 60 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 2HRZE/4HR


  • Intensive phase: 2 months HRZE - once daily
  • Continuation phase: 4 months HR - once daily

Adults will be treated with fixed dose combination (FDC) tablets containing:

Intensive phase (content per tablet)

Isoniazid -75 mg,

Rifampicin - 150 mg,

Pyrazinamide - 400 mg,

Ethambutol - 275 mg

Continuation phase (content per tablet)

Isoniazid 150 mg

Rifampicin 300 mg

*Drug dosing will be adjusted by patient body weight.

Drug: Isoniazid (H)Drug: Rifampicin (R)Drug: Pyrazinamide (Z)Drug: Ethambutol (E)
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Plasma drug levels of Rifampicin
[ Time Frame: 6 Months ]

Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in different study groups
2. Plasma drug levels of Isoniazid
[ Time Frame: 6 Months ]

3. Plasma drug levels of Pyrazinamide
[ Time Frame: 6 Months ]

4. Plasma drug levels of Ethambutol
[ Time Frame: 6 Month ]

Secondary Outcome Measures:
1. Time to negativity of M. tuberculosis
[ Time Frame: 6 Months ]

Time to negativity of M. tuberculosis in relation to drug
2. Genotyping MTB strains
[ Time Frame: 6 Months ]

Genotyping MTB strains in order to see any infection with new wild MTB or mutant strain in the study population
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes

Inclusion Criteria:

  1. Clinical and microbiogical diagnosis of pulmonary TB
  2. Males and females aged >18 years old
  3. Willing to comply with study procedures including residing in the TB centre or nearby for six months
  4. Written informed consent provided by participant

Exclusion Criteria:

  1. TB treatment in the past
  2. Known or suspected pregnancy
  3. Enrolled for TB treatment at one of the study sites
  4. Known hypersensitivity/intolerance to one or more of anti-TB drugs
  5. The MTB strain that shown resistant to Rifampicin, which is the precursor marker of MDR TB detected by a MTB/Rif Xpert Assay
  6. Biochemistry test result:
    1. Creatinine > 3 x upper limit of normal (ULN)
    2. bilirubin > 2.5 x ULN
    3. AST and/or ALT > 5 x ULN
  7. Refuse to take HIV testing
  8. The diagnosed TB patients who choose to take the treatment at a Thai hospital or a hospital in Myanmar
  9. The proven non-TB patients by clinical and microbiological diagnosis.
Open or close this module Contacts/Locations
Central Contact Person: Dr. Thomas Pouplin, PhD
Telephone: 66 2 203 6333
Central Contact Backup: Professor Francois Nosten, MD, PhD
Telephone: +66 5 554 5021
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Available IPD/Information:

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