PK of Levofloxacin in MDR-TB Patients

Multi-drug Resistant Tuberculosis Clinical Trial

Official title:

Pharmacokinetics of Levofloxacin in MDR-TB Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03000517
• Other study ID #: LFX/V0.1
• Status: Completed
• Phase: N/A
• First received: September 1, 2016
• Last updated: January 24, 2018
• Start date: May 4, 2016
• Est. completion date: January 24, 2018

Study information

• Verified date: January 2018
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 24, 2018
• Est. primary completion date: October 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multi-drug Resistant Tuberculosis
• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Locations

Country	Name	City	State
Nepal	German Nepal Tuberculosis Project Clinic (GENETUP)	Kalimati	Kathmandu

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Nepal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC	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.	Period I (15-30) day and Period II (45-60) day