Clinical trial NCT02121314: HRZE Fasted/Fed in Newly Diagnosed TB
Official title: The Influence of Fasting and Food on the Pharmacokinetics of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol in Newly Diagnosed TB Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis
Keywords: TB
bioavailability
HRZE
fasting
fed
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: University of Groningen
name: Gadjah Mada University
First posted: 2014-04-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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)

Primary outcomes:
measure: pharmacokinetics
timeFrame: 3 days - week 1 and week 8
measure: pharmacokinetics (AUC0-8, Cmax, and Tmax) of HRZE
timeFrame: 11 time points, 3 consecutive days - wk 1 & 8
Secondary outcomes:
measure: To evaluate adverse events of HRZE, week 1 and 8 - while taking food or not
timeFrame: week 1 - week 8
Other outcomes:
measure: confounding factors for primary and secondary outcomes
timeFrame: weeks 1 and 8
Locations:
city: Yogyakarta
country: Indonesia
facility: Sardjito Central Hospital
Study officials:
References:
citation: Saktiawati AMI, Harkema M, Setyawan A, Subronto YW, Sumardi, Stienstra Y, Aarnoutse RE, Magis-Escurra C, Kosterink JGW, van der Werf TS, Alffenaar JC, Sturkenboom MGG. Optimal Sampling Strategies for Therapeutic Drug Monitoring of First-Line Tuberculosis Drugs in Patients with Tuberculosis. Clin Pharmacokinet. 2019 Nov;58(11):1445-1454. doi: 10.1007/s40262-019-00763-3.
citation: Saktiawati AM, Sturkenboom MG, Stienstra Y, Subronto YW, Sumardi, Kosterink JG, van der Werf TS, Alffenaar JW. Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients: a randomized cross-over trial. J Antimicrob Chemother. 2016 Mar;71(3):703-10. doi: 10.1093/jac/dkv394. Epub 2015 Dec 11.