- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02457208
PK Study of Anti-TB Drugs
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Tak
-
Mae Sot, Tak, Thailand, 63110
- Shoklo Malaria Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 2HRZE/4HR
2HRZE/4HR
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma drug levels of Rifampicin
Time Frame: 6 Months
|
Rifampicin, Isoniazid, Pyrazinamide and Ethambutol in different study groups
|
6 Months
|
Plasma drug levels of Isoniazid
Time Frame: 6 Months
|
6 Months
|
|
Plasma drug levels of Pyrazinamide
Time Frame: 6 Months
|
6 Months
|
|
Plasma drug levels of Ethambutol
Time Frame: 6 Month
|
6 Month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to negativity of M. tuberculosis
Time Frame: 6 Months
|
Time to negativity of M. tuberculosis in relation to drug
|
6 Months
|
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
|
6 Months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Gram-Positive Bacterial Infections
- Actinomycetales Infections
- Mycobacterium Infections
- Tuberculosis
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antimetabolites
- Hypolipidemic Agents
- Lipid Regulating Agents
- Anti-Bacterial Agents
- Leprostatic Agents
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- Antitubercular Agents
- Antibiotics, Antitubercular
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C9 Inducers
- Fatty Acid Synthesis Inhibitors
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
Other Study ID Numbers
- SMRU1407
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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