TuberculosisPhase 1NCT02457208
PK Study of Anti-TB Drugs
A Phase 1 study testing Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z) in people with Tuberculosis, run by University of Oxford at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteThailand
- Study dates
- 7 Jul 2015to 14 Jan 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Clinical and microbiogical diagnosis of pulmonary TB
- Males and females aged >18 years old
- Willing to comply with study procedures including residing in the TB centre or nearby for six months
- Written informed consent provided by participant
Who cannot join
- TB treatment in the past
- Known or suspected pregnancy
- Enrolled for TB treatment at one of the study sites
- Known hypersensitivity/intolerance to one or more of anti-TB drugs
- The MTB strain that shown resistant to Rifampicin, which is the precursor marker of MDR TB detected by a MTB/Rif Xpert Assay
- Biochemistry test result:
Show all 12Show fewer
- Creatinine > 3 x upper limit of normal (ULN)
- bilirubin > 2.5 x ULN
- AST and/or ALT > 5 x ULN
- Refuse to take HIV testing
- The diagnosed TB patients who choose to take the treatment at a Thai hospital or a hospital in Myanmar
- The proven non-TB patients by clinical and microbiological diagnosis.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E)
- Keywords
- pharmacokinetics
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid (H)Drug
Rifampicin (R)Drug
Pyrazinamide (Z)Drug
Ethambutol (E)Drug
| Study group | Role | What they receive |
|---|---|---|
| 2HRZE/4HR | 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. Receives: Drug: Isoniazid (H); Drug: Rifampicin (R); Drug: Pyrazinamide (Z); Drug: Ethambutol (E) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma drug levels of Rifampicin
Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in different study groups
Measured: 6 Months
Plasma drug levels of Isoniazid
Measured: 6 Months
Plasma drug levels of Pyrazinamide
Measured: 6 Months
Plasma drug levels of Ethambutol
Measured: 6 Month
Secondary outcomes (2)
Time to negativity of M. tuberculosis
Time to negativity of M. tuberculosis in relation to drug
Measured: 6 Months
Genotyping MTB strains
Genotyping MTB strains in order to see any infection with new wild MTB or mutant strain in the study population
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study start7 Jul 2015
- Primary completion14 Jan 2018
- Study completion14 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457208
- Sponsor's protocol ID
- SMRU1407
- Status last verified
- Oct 2018
- First submitted
- 22 Apr 2015
- Last updated
- 3 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Phyo AP, Hoglund RM, Saito M, Thi SS, Swe LL, Chotsiri P, Aung HKK, Tun WPP, Maung BM, Pateekham C, Watthanaworawit W, Gornsawun G, White NJ, Nosten F, Tarning J. Altered Pharmacokinetics and Delayed Sputum Conversion in Tuberculosis Patients Co-Infected With HIV. Trop Med Int Health. 2026 May 19. doi: 10.1111/tmi.70165. Online ahead of print.
PubMed 42156227
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02457208
- Acronym / sponsor ID
- SMRU1407
- Conditions
- Tuberculosis
- Keywords
- pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 7 Jul 2015 (actual)
- Primary completion
- 14 Jan 2018 (actual)
- Study completion
- 14 Jan 2018 (actual)
- First posted
- 29 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2HRZE/4HR | Experimental | Drug: Isoniazid (H), Drug: Rifampicin (R), Drug: Pyrazinamide (Z), Drug: Ethambutol (E)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical and microbiogical diagnosis of pulmonary TB
- Males and females aged >18 years old
- Willing to comply with study procedures including residing in the TB centre or nearby for six months
- Written informed consent provided by participant
Key exclusion criteria (12 listed)
- TB treatment in the past
- Known or suspected pregnancy
- Enrolled for TB treatment at one of the study sites
- Known hypersensitivity/intolerance to one or more of anti-TB drugs
- The MTB strain that shown resistant to Rifampicin, which is the precursor marker of MDR TB detected by a MTB/Rif Xpert Assay
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoniazid (H) | Drug | 2HRZE/4HR |
| Rifampicin (R) | Drug | 2HRZE/4HR |
| Pyrazinamide (Z) | Drug | 2HRZE/4HR |
| Ethambutol (E) | Drug | 2HRZE/4HR |
Primary outcome
Plasma drug levels of Rifampicin
Time frame: 6 Months
Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in different study groups
Plasma drug levels of Isoniazid
Time frame: 6 Months
Plasma drug levels of Pyrazinamide
Time frame: 6 Months
Plasma drug levels of Ethambutol
Time frame: 6 Month
2 secondary outcomes
Time to negativity of M. tuberculosis
Time frame: 6 Months
Genotyping MTB strains
Time frame: 6 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2018.
- Derived from this study: PubMed 42156227Phyo AP, Hoglund RM, Saito M, Thi SS, Swe LL, Chotsiri P, Aung HKK, Tun WPP, Maung BM, Pateekham C, Watthanaworawit W, Gornsawun G, White NJ, Nosten F, Tarning J. Altered Pharmacokinetics and Delayed Sputum Conversion in Tuberculosis Patients Co-Infected With HIV. Trop Med Int Health. 2026 May 19. doi: 10.1111/tmi.70165. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isoniazid (H), Rifampicin (R) and Pyrazinamide (Z) in people with Tuberculosis, run by University of Oxford at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma drug levels of Rifampicin (time frame: 6 Months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02457208, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2018.