Tuberculosis
Conditions
Keywords
TB, bioavailability, HRZE, fasting, fed
Brief summary
WHO recommends to take TB drugs while fasting: if TB drugs are taken with food, perhaps drug concentrations are too low; on the other hand: if this is not tolerated, drugs could also be taken with food. Do lower drug concentrations - with improved adherence to therapy - outweigh the disadvantage of lower drug blood concentrations over time? How exactly do the drug concentrations over time (pharmacokinetics) compare between fasting and fed conditions, especially in the early stage of TB treatment when patients are relatively sick, and relatively poorly tolerate TB drugs?
Detailed description
To evaluate the influence of concomitant food ingestion on the pharmacokinetics of HRZE in newly diagnosed TB patients To evaluate the influence of early disease on the PK parameters of HRZE in TB patients To compare the pharmacokinetics of HRZE in the early stage of disease with the pharmacokinetics of HRZE in more stable condition in newly diagnosed TB patients To evaluate adverse events of HRZE in TB patients
Interventions
DRUGintravenous administration of 1st line TB drugs, day 1
TB drugs IV on day 1 for calculation of bioavailability while fasting or fed
Sponsors
University of Groningen
Gadjah Mada University
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with TB who are starting with HRZE therapy * Age \> 18 years old * Written informed consent
Exclusion criteria
* Use of antacids, which cannot be discontinued for study days * Active, unstable hepatic disease (with jaundice, HRZ)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pharmacokinetics | 3 days - week 1 and week 8 | pharmacokinetics (AUC0-8, Cmax, and Tmax); comparison between TB patients who take HRZE concomitant with food and TB patients who take HRZE concomitant without food, weeks 1 and 8 of treatment |
| pharmacokinetics (AUC0-8, Cmax, and Tmax) of HRZE | 11 time points, 3 consecutive days - wk 1 & 8 | PK curves from venous blood specimens sampled from indwelling venous catheter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate adverse events of HRZE, week 1 and 8 - while taking food or not | week 1 - week 8 | tolerance - acceptance; vomiting, refusal |
Other
| Measure | Time frame | Description |
|---|---|---|
| confounding factors for primary and secondary outcomes | weeks 1 and 8 | Parameters which may influence the pharmacokinetics of HRZE will be measured at start and end of the study. * BMI, i.e. body weight and length * age * gender * ethnicity * co-morbidity, for instance HIV/AIDS, diabetes (only at start) * co-medication: especially HIV medication, prednisolone (may lower INH concentration), antacids (may lower absorption of HRE concentration) * chemistry: liver function, renal function, hemoglobulin, albumin, bilirubin * pharmacogenetics |
Countries
Indonesia
Outcome results
None listed