HRZE Fasted/Fed in Newly Diagnosed TB

Phase 2

Completed

• Conditions: Tuberculosis
• Interventions: Drug: intravenous administration of 1st line TB drugs, day 1

• Registration Number: NCT02121314
• Lead Sponsor: University Medical Center Groningen

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

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2014-01-25
• Primary Completion: 2014-04
• Study First Submitted QC: 2014-04-22
• Study First Posted: 2014-04-23
• Study Completion: 2014-06
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-07
• Last Update Posted: 2015-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fasting-Fed	intravenous administration of 1st line TB drugs, day 1	blood sampling on 3 consecutive days; by randomization, drug treatment as follows: day 1, HRZE as iv therapy; on day 2, HRZE as oral therapy in fasting condition (2 hours before meals); and on day 3 HRZE as oral therapy in fed condition (after meals).
Fed-Fasting	intravenous administration of 1st line TB drugs, day 1	blood sampling on 3 consecutive days; by randomization, drug treatment as follows: day 1, HRZE therapy as iv therapy; day 2, HRZE as oral therapy in fed condition, and on day 3, HRZE as oral therapy in fasting condition

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
To evaluate adverse events of HRZE, week 1 and 8 - while taking food or not	week 1 - week 8	tolerance - acceptance; vomiting, refusal

Trial Locations

Locations (1)

Sardjito Central Hospital; 🇮🇩 Yogyakarta, Indonesia