Tuberculosis MedDRA version: 12.1 Level: LLT Classification code 10044755 Term: Tuberculosis
Conditions
Interventions
Trade Name: Avelox
Pharmaceutical Form: Tablet
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: *Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture *Starting treatment with MFX in a dose of 400 mg as part of their TB treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: * Contra-indication for MFX; Baseline QTc-interval > 450 msec * History of resuscitation * History of ventricular tachycardia (including Torsades de Pointes) * Family history of sudden cardiac death or Torsades de Pointes * Additional risk factors for Torsades de Pointes (including known heart failure, Left ventricular hypertrophy) * Use of concomitant treatment with QT/QTc prolonging drugs (including anti-dysrhythmics class IA and III, antipsychotics, tricyclic antidepressants or the antihistaminic drug terfenadine) * Abnormal electrolytes (K, Mg, Na, Ca) * Abnormal cardiac repolarisation on screening/baseline ECG * History of adverse events to fluoroquinolones * HIV co-infection * RIF treatment during last 3 weeks before start of the study. After a washout period of 3 weeks the patient can be included.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this prospective clinical trial is to compare pharmacokinetics and safety and tolerability of a standard dose (400 mg) with an escalated dose of 600 and 800 mg MFX;Secondary Objective: *To evaluate limited sampling strategies based on a pharmacokinetic population model to predict MFX AUC0-24h *To evaluate the correlation between MFX concentration (mg/L) and QT interval (msec) *To evaluate a genetic risk score for the prediction of MFX induced QT prolongation ;Primary end point(s): Pharmacokinetics * Bound AUC0-24h/MIC ratio; the percentage of patients who will reach an AUC0-24h/MIC ratio of at least 100 after administration of different dosages (400; 600; 800 mg) * Unbound AUC0-24h/MIC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis; the percentage of patients who will reach an unbound AUC0-24h/MIC ratio of at least 60 after administration of different dosages (400; 600; 800 mg) * Bound AUC0-24h/MPC ratio; percentage of patients who will reach an adequate AUC0-24h/MPC ratio of at least 93 after administration of different dosages (400; 600; 800 mg) * Unbound AUC0-24h/MPC ratio as predictive parameter for efficacy of unbound MFX dose escalated treatment of tuberculosis and suppression of MFX resistance; percentage of patients who will reach an unbound AUC0-24h/MPC ratio of at least 53 after administration of different dosages (400; 600; 800 mg) Safety Percentage of patients having adverse effects, including QT interval prolongation, hypersensitive reactions, diarrhoea, vomiting and hepatic or renal injury * QT interval in msec * Percentage of patients developing hepatic toxicity grade = 2 or 3 CTC * Percentage of patients developing renal toxicity grade = 2 CTC | — |
Countries
Netherlands
Outcome results
None listed