Skip to main content
OpenTrials
Completed

NCT Number: NCT01521364

Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients

Future patients might benefit from a combination of linezolid (LIN) and clarithromycin (CLA) in the treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) due to possible synergistic activity as shown in in vitro experiments in different Mycobacteria strains. The investigators observed increased LIN serum levels in three cases after combining LIN and CLA of which the investigators described one in a case report (Bolhuis et al). The investigators suggest to conduct a prospective pharmacokinetic study in MDR- and XDR-TB patients to quantify the above described interaction between LIN and CLA.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Multidrug-resistant Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Extensively Drug-Resistant Tuberculosis Gram-Positive Bacterial Infections Infections Mycobacterium Infections Tuberculosis Tuberculosis, Multidrug-Resistant

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Tuberculosis Center Beatrixoord

Haren, Provincie Groningen, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥18 years old
  • Signed informed consent
  • Diagnosis of MDR/XDR-TB confirmed with standard microbiological criteria (culture-based, molecular or both)
  • Treatment with linezolid 300mg twice daily per os.

Exclusion criteria

  • Hypersensitivity to: linezolid, clarithromycin, erythromycin, or any macrolide antibiotics, or any of the excipients of linezolid or clarithromycin.
  • Concomitant use with astemizole, cisapride, ergotamine derivatives (dihydroergotamine, ergotamine), monoamine oxidase inhibitors (phenelzine, isocarboxazid, selegiline, or moclobemide), pimozide, or terfenadine.
  • Pregnancy or breast-feeding.
  • Hypokalemia
  • Concomitant use of other P-gp inhibitors/inducers, e.g. amiodarone, verapamil, digoxin, tipranavir/ritonavir, lovastatin, tariquidar, itraconazole, dipyridamol, erythromycin, ritonavir, quinidine.

Treatment and study plan

Addition of different doses of clarithromycin.

Drug

At week 1, 250mg clarithromycin once a day will be added to linezolid therapy during two weeks.

At week 3, 500mg clarithromycin once a day will be added to linezolid therapy during to weeks.

Other names: Clarithromycin, 250/500mg (Pharmachemie) RVG 029081/029082

Primary outcomes

  1. Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Plasma After Addition of 0mg, 250mg, or 500mg Clarithromycin (CLA).

    Time frame: At week 1 (baseline), week 3 (250mg clarithromycin), and week 5(500mg clarithromycin).

    The AUCs of linezolid will be measured at 3 time points after addition of 3 different clarithromycin dosages.

    Samples were obtained before doseing and 1h, 2h, 3h, 4h, 8h, and 12h after administration of linezolid (and claritromycin depending on the period).

Secondary outcomes

  1. Linezolid (LIN) and Clarithromycin (CLA) Pharmacokinetic Parameters, e.g. Tmax, Cmax, Cmin, T1/2, Cl.

    Time frame: At week 1 (baseline), week 3 (250mg clarithromycin), and week 5 (500mg clarithromycin) and week 6 (baseline).

  2. Number of Patients With Adverse Events (AEs)

    Time frame: Up to week 6

    To assess short-term safety and tolerability when combining linezolid (LIN) with clarithromycin (CLA) by monitoring AEs, i.e. gastro-intestinal effects, hyperlactatemia, haematological abnormalities and neuropathy.

  3. Pharmacokinetic Parameters, e.g. Tmax, T1/2, Cmax, Cmin, Cl, of Anti-TB Drugs That Are Co-administered as Part of the Continued Standard Care.

    Time frame: At week 1 (baseline), week 3 (250mg clarithromycin) and week 5 (500mg clarithromycin)

  4. Area Under the Time Concentration Curve (AUC0-12h) of Linezolid in Saliva.

    Time frame: At week 3 (after co-administration of 250mg clarithromycin)

    The data will be used to clinically validate the analysis linezolid in saliva as surrogate marker for linezolid in plasma.

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Registry information

Official study title

The Pharmacokinetic Effect of Clarithromycin on the AUC0-12h of Linezolid in Multidrug-resistant and Extensively Drug-resistant Tuberculosis (MDR/XDR-TB) Patients

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Jan 30, 2012
Registry last updated
Jul 1, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.