DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis
ConditionTuberculosis, Pulmonary
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorKarolinska Institutet
About this trial
The goal of this observational study is to investigate whether model-informed precision dosing (MIPD), as a clinical support for early individualised dosing in addition to the national TB care program, can optimise the drug exposure of TB drugs during TB treatment.
Main research questions:
In adult patients with drug-susceptible pulmonary tuberculosis, can current dose recommendations and information received from MIPD help clinicians in a timely manner to optimise the drug exposure of TB drugs in the early treatment phase, i.e., the time from PK sampling to dose adjustment (keep or adjust dose)?
Specific aims
I. To perform a process evaluation of early MIPD for rifampicin, isoniazid, pyrazinamide and ethambutol during active TB treatment.
II. To study the target attainment of first-line TB drugs with MIPD.
III. To evaluate model precision of predicted versus detected drug concentrations.
Drug concentrations will be measured in study participants during TB treatment, and drug exposure and the optimal dose will be predicted by MIPD using pharmacokinetic population models.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult persons ≥18 years with confirmed pulmonary TB (established through Mtb cultures or PCR for Mtb by clinical routine)
Ongoing or planned treatment of TB that includes rifampin
Written informed consent
Disqualifiers
TB treatment with rifampin for longer than 8 weeks prior to inclusion
TB treatment with intravenous rifampin (including patients treated at an intensive care unit (ICU) or patients with cerebral TB)
TDM of rifampin has already been performed (>24 h before inclusion) by clinical routine
Study participants with extrapulmonary TB without pulmonary TB.
Trial population
The inclusion of study participants will be done prospectively at two hospitals included in the study sites (Karolinska University Hospital and Region Östergötland). Only patients with pulmonary TB will be included as the MIPD models have been developed using data sets of pulmonary TB and not for extrapulmonary TB. Participants who are unable to give an informed consent (e.g. persons with severe dementia) will not be included. The investigators will include at least 30 participants. Blood samples for drug concentration analysis will be performed 2+4 hours postdose at 2 -3 occasions during the study period and measure by a validated HPLC method at Clinical Pharmacology Laboratories in the regions.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
MIPD
Other interventionThis is a non-inverventional study
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Pulmonary tuberculosis1 intervention
Trial outcomes
Primary outcomes
1
Proportion of predicted dose
Proportion of participants with predicted doses of rifampicin, isoniazid and/or pyrazinamide within 5 days from sampling (%)
Time frame
Within the first 5 days from samplingSecondary outcomes
1
Proportion reaching predicted drug exposure
For participants with dose-predicted treatment, proportion who will reach the target levels for rifampicin, isoniazid and/or pyrazinamide after MIPD
Time frame
Through study completion, an average of one month2
Model precision
Precision of the model comparing predicted drug levels to the detected drug levels (%)
Time frame
Through study completion, an average of one monthSponsors and contacts
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Karolinska Institutet
Lead sponsor
Karolinska University Hospital
Collaborator
Region Östergötland
Collaborator
Source ClinicalTrials.gov