Clinical trial NCT03000517: PK of Levofloxacin in MDR-TB Patients
Official title: Pharmacokinetics of Levofloxacin in MDR-TB Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multi-drug Resistant Tuberculosis
Keywords: levofloxacin
multi-drug resistant TB
pharmacokinetics
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2016-12-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with previously treated or newly diagnosed MDR-TB who are at the end of first month(15-30th day) and second month (45-60th day) of their treatment.

Brief summary: The emergence and spread of multi-drug resistant and extensively-drug resistant strains of Mycobacterium tuberculosis (MDR/XDR-TB) have posed a great threat to global TB control and elimination, limiting treatment success rate at worrisome 50% for MDR-TB. Among various factors contributing to the development of drug resistance, low drug exposure is well recognized. To overcome this, either new drugs have to be developed or the dose of currently used therapy be optimized, or both. Fluoroquinolones (levofloxacin and moxifloxacin) and aminoglycosides are important drugs in the MDR-TB treatment regimen. Development of acquired drug resistance to these drugs could complicate and narrow down the available options, and further exacerbate to pre-XDR and XDR-TB.

Objective:

The main objective of this prospective clinical study is to understand the pharmacokinetics of levofloxacin in MDR-TB patients, receiving standard dosage (750-1250mg) based on the body weight and correlate drug exposure, with treatment outcomes.

Study design:

A prospective pharmacokinetic study

Study population: 20 MDR-TB patients

Intervention: Patients receive once daily oral dosing of levofloxacin (750-1250mg) based on the body weight, under MDR-TB treatment regimen of Nepal.

Main study parameters/end points:

The pharmacokinetic parameters(Vd, CL, AUC etc.) of levofloxacin are the primary end points of the study. The Cmax/MIC and AUC0-24h/MIC ratios are the best predictive parameters for efficacy of levofloxacin treatment and will be estimated. Pharmacokinetics will be evaluated in plasma and in oral fluid


Eligibility criteria: Inclusion Criteria:

* Patient with TB, with Mycobacterium tuberculosis by culture/ Gene Xpert
* Patient is 18 years or older with newly diagnosed or previously treated MDR-TB
* Patient with sputum smear positive for acid-fast bacilli or sputum smear negative but Gene Xpert (MTB/RIF) positive, and resistant to both isoniazid and rifampicin
* Patients with MDR-TB receiving levofloxacin as a part of MDR-TB regimen

Exclusion Criteria:

* Patient with neurologic or severe extra-pulmonary manifestations of tuberculosis
* Pregnant women or breast feeding mothers with MDR-TB
* Patients with diminished renal functions or on medications for the treatment of renal disorders
* Body weight \<35 kg
* Patients treated with aluminium- and magnesium containing antacids and ferrous sulphates, cimetidine and probenecid, theophylline, warfarin, zidovudine, digoxin or cyclosporine.

Primary outcomes:
measure: AUC
timeFrame: Period I (15-30) day and Period II (45-60) day
Secondary outcomes:
Other outcomes:
Locations:
city: Kalimati
country: Nepal
facility: German Nepal Tuberculosis Project Clinic (GENETUP)
state: Kathmandu
Study officials:
affiliation: University Medical Center Groningen, University of Groningen
name: Jan-Willem Alffenaar
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghimire S, Maharjan B, Jongedijk EM, Kosterink JGW, Ghimire GR, Touw DJ, van der Werf TS, Shrestha B, Alffenaar JC. Evaluation of Saliva as a Potential Alternative Sampling Matrix for Therapeutic Drug Monitoring of Levofloxacin in Patients with Multidrug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02379-18. doi: 10.1128/AAC.02379-18. Print 2019 May.