PK of Levofloxacin in MDR-TB Patients

NCT03000517 | Completed

• 1 other identifier: LFX/V0.1
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Multi-drug Resistant Tuberculosis

Keywords

levofloxacin; multi-drug resistant TB; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

German Nepal Tuberculosis Project Clinic (GENETUP)

Kalimati, Kathmandu, 1494, Nepal

Location

Related Publications (1)

• 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.

  PMID: 30782999 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and saliva samples of MDR-TB patients on 0 hr premedication and 1,2,4,8 hrs post mediation.

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Jan-Willem Alffenaar

  University Medical Center Groningen, University of Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD PharmD Clinical Pharmacologist

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: December 22, 2016
• Study Start: May 4, 2016
• Primary Completion: October 27, 2017
• Study Completion: January 24, 2018
• Last Updated: January 25, 2018

Record last verified: 2018-01

Locations

NE (1)