DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis

Karolinska Institute

Status: Enrolling

Conditions: Tuberculosis, Pulmonary

Treatments: Other: MIPD

Study type: Observational

Funder types: Other

Identifiers

NCT06585358

4-1624/2023

Details and patient eligibility

About

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.

Full description

Background:

Individualised treatment for tuberculosis (TB) to improve treatment outcome has still some substantial obstacles to pass before becoming a reality in clinical practice. Previous studies, including studies from the study research group, have shown that lower than recommended drug concentrations of TB drugs are common, and affect treatment outcome. Despite this, lower than recommended doses are often prescribed by clinicians. Adequate drug doses should be ensured as early as possible in the intensive phase when the bacterial load is high. Simple therapeutic drug monitoring (TDM) at the time of steady state of TB drugs are used in many clinical settings today, but time to dose adjustments to avoid suboptimal drug levels is typically several weeks. However, pharmacokinetic models are in place to guide individualised drug dosing by Model-Informed Precision Dosing (MIPD) already from the first days of treatment. MIPD, in combination with currently recommended dose recommendations, can be used to derive the most efficacious and safe dose for a patient. A similar approach has been implemented for dosing of vancomycin in children but has not been used in a clinical setting in the field of TB. This study will evaluate the logistics and dose regimens when clinicians are given the current dose recommendations of the first-line drugs rifampicin, isoniazid and pyrazinamide, as well as the results of the MIPD, for patients with active pulmonary TB.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

1. Adult persons ≥18 years with confirmed pulmonary TB (established through Mtb cultures or PCR for Mtb by clinical routine)
2. Ongoing or planned treatment of TB that includes rifampin
3. Written informed consent

Exclusion criteria

1. TB treatment with rifampin for longer than 8 weeks prior to inclusion
2. TB treatment with intravenous rifampin (including patients treated at an intensive care unit (ICU) or patients with cerebral TB)
3. TDM of rifampin has already been performed (>24 h before inclusion) by clinical routine
4. Study participants with extrapulmonary TB without pulmonary TB.

Trial design

30 participants in 1 patient group

Pulmonary tuberculosis

Treatment:

Other: MIPD