PK of Levofloxacin in MDR-TB Patients

Completed

• Conditions: Multi-drug Resistant Tuberculosis

• Registration Number: NCT03000517
• Lead Sponsor: University Medical Center Groningen

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

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-04
• Study First Submitted: 2016-09-01
• Study First Submitted QC: 2016-12-19
• Study First Posted: 2016-12-22
• Primary Completion: 2017-10-27
• Status Verified: 2018-01
• Study Completion: 2018-01-24
• Last Update Submitted: 2018-01-24
• Last Update Posted: 2018-01-25

Recruitment & Eligibility

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

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
AUC	Period I (15-30) day and Period II (45-60) day	The main objective of this prospective clinical trial is to evaluate the levofloxacin exposures (AUC) of a standard dose (750-1250mg) in plasma and saliva of MDR-TB patients.

Trial Locations

Locations (1)

German Nepal Tuberculosis Project Clinic (GENETUP); 🇳🇵 Kalimati, Kathmandu, Nepal