The Role of Therapeutic Drug Monitoring in Tuberculosis - a Pilot Study

Completed

• Conditions: Active Tuberculosis

• Registration Number: NCT02042261
• Lead Sponsor: Thomas Schon

Brief Summary

Drug resistant TB is increasing and in order to enchance the efficacy of the current drugs, individualized therapy using plasma drug concentrations and minimal inhibitory concentration (MIC) determination may be of importance. This concept is defined as therapeutic drug monitoring (TDM).

In this pilot study our hypothesis is that the ratio between MIC and drug concentration data is correlated to the bacterial load measured as time to positive liquid culture (TTP).

In two sites in Sweden (Linköping and Karolinska Hospital Solna, Stockholm), 25 patients with pulmonary tuberculosis will be recruited. MIC-determination of Mycobacterium tuberculosis will be performed in BACTEC 960 MGIT and drug concentration will be determined at 2, 4 and 12 weeks after treatment initiation using LC-MS/MS methodology. Sputum cultures will be obtained at 0, 2 days, 7 days, 2 weeks, 4 weeks and 8 weeks and TTP will be measured in duplicate samples. Clinical follow up according to WHO criteria will be performed 1 year after completion of treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2014-01-20
• Study First Submitted QC: 2014-01-20
• Study First Posted: 2014-01-22
• Primary Completion: 2015-11
• Status Verified: 2016-03
• Study Completion: 2016-03
• Last Update Submitted: 2016-03-01
• Last Update Posted: 2016-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

Age>18 years, culture verified tuberculosis

Exclusion Criteria

Other infectious diseases other than HIV or tuberculosis

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rifampicin concentration in relationship to MIC over 10	2 weeks

Secondary Outcome Measures

Name	Time	Method
TB-score in relation to rifampicin, isoniazid and pyrazinamid concentration week 2	8 weeks
Time to positive Culture (TTP) in relation to isoniazid, ethambutol and pyrazinamid serum concentration and minimal inhibitory concentration (MIC)	2 and 8 weeks
Time to positive Culture (TTP) in relation to rifampicin serum concentration and minimal inhibitory concentration (MIC)	2weeks
Cure rate on Clinical follow up (according to WHO criteria) in relation to rifampicin concentration at week 2	1 year
Sputum Culture conversion in relation to rifampicin, isoniazid and pyrazinamid concentration week 2	2 and 8 weeks

Trial Locations

Locations (2)

Dept of Infectious Diseases; 🇸🇪 Linköping, Sweden

Dept of Infectious Diseases, TB-unit, Karolinska Hospital; 🇸🇪 Stockholm, Sweden