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

NCT ID: NCT06585358

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-11-01

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Tuberculosis, Pulmonary

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Pulmonary tuberculosis

MIPD

Intervention Type OTHER

This is a non-inverventional study

Interventions

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MIPD

This is a non-inverventional study

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Karolinska University Hospital

OTHER

Sponsor Role collaborator

Region Östergötland

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Lina Davies Forsman

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lina Davies Forsman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Linköping University Hospital

Linköping, , Sweden

Site Status RECRUITING

Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Lina Davies Forsman, MD, PhD, Associate Professor

Role: CONTACT

08-12370000

Katarina Niward, MD, PhD

Role: CONTACT

+46 10 103 00 00

Facility Contacts

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Katarina Niward Senior Consultant, PhD, MD

Role: primary

Lina Davies Forsman Senior Consultant, Ass. Professor, PhD, MD

Role: primary

+ 46 8 123 70 000

Role: backup

References

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Abdulla A, Edwina EE, Flint RB, Allegaert K, Wildschut ED, Koch BCP, de Hoog M. Model-Informed Precision Dosing of Antibiotics in Pediatric Patients: A Narrative Review. Front Pediatr. 2021 Feb 23;9:624639. doi: 10.3389/fped.2021.624639. eCollection 2021.

Reference Type BACKGROUND
PMID: 33708753 (View on PubMed)

Azuma J, Ohno M, Kubota R, Yokota S, Nagai T, Tsuyuguchi K, Okuda Y, Takashima T, Kamimura S, Fujio Y, Kawase I; Pharmacogenetics-based tuberculosis therapy research group. NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol. 2013 May;69(5):1091-101. doi: 10.1007/s00228-012-1429-9. Epub 2012 Nov 14.

Reference Type BACKGROUND
PMID: 23150149 (View on PubMed)

Pasipanodya JG, McIlleron H, Burger A, Wash PA, Smith P, Gumbo T. Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J Infect Dis. 2013 Nov 1;208(9):1464-73. doi: 10.1093/infdis/jit352. Epub 2013 Jul 29.

Reference Type BACKGROUND
PMID: 23901086 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30124844 (View on PubMed)

Other Identifiers

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4-1624/2023

Identifier Type: -

Identifier Source: org_study_id

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