The goal of this clinical trial is to compare an optimized dose (1800 mg) of rifampicin to standard dose (450 mg if patient \<50 kg and 600 mg if patient \>50kg) of rifampicin in tuberculosis patients. The main questions it aims to answer are: * To compare the incidence of hepatotoxicity occurs in the optimized dose vs standard dose arm * To compare any adverse events occur in the optimized dose vs standard dose arm * To compare final treatment outcome at the end of treatment according to WHO definitions of cure in the optimized dose regimen versus the standard dose regimen. * To compare two and three months culture conversion rates in the optimized dose regimen versus the standard dose regimen. * To describe and compare the steady-state plasma pharmacokinetics of the optimized dose regimen versus the standard dose regimen. Participants will be given an optimized dose of 1800 mg of rifampicin daily. Researchers will compare the optimized and standard dose to see if more hepatotoxicity occurs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
164
Optimized dose of rifampicin
Standard dose rifampicin
ASL Città di Torino
Turin, Italy
RECRUITINGRadboud University Medical Centre
Nijmegen, Netherlands
RECRUITINGIncidence of hepatotoxicity
How often does hepatotoxicity occur in patients with optimized dose rifampicin vs standard dose rifampicin
Time frame: 26 weeks
Adverse events
The proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin will be compared between treatment arms.
Time frame: 26 weeks
Treatment outcome
Final treatment outcome at the end of treatment according to WHO definitions of cure will be compared between treatment arms
Time frame: 26 weeks
Culture conversion rate
Two and three months culture conversion rates will be compared between treatment arms.
Time frame: 2 and 3 months post-treatment initiation
PK parameter, AUC0-24
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The AUC0-24 will be determined using sparse PK sampling.
Time frame: 2 Weeks
PK parameter, Cmax
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The maximum concentration will be determined using sparse PK sampling.
Time frame: 2 Weeks
PK parameter, Tmax
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The time to maximum concentration will be determined using sparse PK sampling.
Time frame: 2 Weeks
PK parameter, Clearance
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The clearance of rifampicin will be determined using sparse PK sampling.
Time frame: 2 Weeks
PK parameter, Volume of distribution
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The volume of distribution of rifampicin will be determined using sparse PK sampling.
Time frame: 2 Weeks
PK parameter, T1/2
Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The half life of rifampicin will be determined using sparse PK sampling.
Time frame: 2 Weeks
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