Clinical trial NCT02042261: The Role of Therapeutic Drug Monitoring in Tuberculosis - a Pilot Study
Official title: The Role of Therapeutic Drug Monitoring in Tuberculosis - a Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Active Tuberculosis
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: University Hospital, Linkoeping
name: Karolinska University Hospital
First posted: 2014-01-22
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly diagnosed patients with culture verified tuberculosis

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.


Eligibility criteria: Inclusion Criteria:

Age\>18 years, culture verified tuberculosis

Exclusion Criteria:

Other infectious diseases other than HIV or tuberculosis

Primary outcomes:
measure: Rifampicin concentration in relationship to MIC over 10
timeFrame: 2 weeks
Secondary outcomes:
measure: Cure rate on Clinical follow up (according to WHO criteria) in relation to rifampicin concentration at week 2
timeFrame: 1 year
measure: Sputum Culture conversion in relation to rifampicin, isoniazid and pyrazinamid concentration week 2
timeFrame: 2 and 8 weeks
measure: TB-score in relation to rifampicin, isoniazid and pyrazinamid concentration week 2
timeFrame: 8 weeks
measure: Time to positive Culture (TTP) in relation to isoniazid, ethambutol and pyrazinamid serum concentration and minimal inhibitory concentration (MIC)
timeFrame: 2 and 8 weeks
measure: Time to positive Culture (TTP) in relation to rifampicin serum concentration and minimal inhibitory concentration (MIC)
timeFrame: 2weeks
Other outcomes:
Locations:
city: Linköping
country: Sweden
facility: Dept of Infectious Diseases
city: Stockholm
country: Sweden
facility: Dept of Infectious Diseases, TB-unit, Karolinska Hospital
Study officials:
affiliation: Linkoeping University
name: Katarina Niward, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Niward K, Davies Forsman L, Bruchfeld J, Chryssanthou E, Carlstrom O, Alomari T, Carlsson B, Pohanka A, Mansjo M, Jonsson Nordvall M, Johansson AG, Eliasson E, Werngren J, Paues J, Simonsson USH, Schon T. Distribution of plasma concentrations of first-line anti-TB drugs and individual MICs: a prospective cohort study in a low endemic setting. J Antimicrob Chemother. 2018 Oct 1;73(10):2838-2845. doi: 10.1093/jac/dky268.