Tuberculosis, PulmonaryDoseTBNCT06585358
DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis
An observational study of Tuberculosis, Pulmonary, run by Karolinska Institutet at 2 sites in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Pulmonary
- What is being tested?
- MIPD
- How many people
- 30 participants
- Where
- 2 sitesSweden
- Study dates
- 1 Nov 2025to Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study 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.
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden2 sites, 2 recruiting
- Recruiting
Linköping University Hospital
Linköping
Katarina Niward Senior Consultant, PhD, MD, katarina.niward@liu.se
Katarina Niward, PhD
- Recruiting
Karolinska University Hospital
Stockholm, 17177
Lina Davies Forsman Senior Consultant, Ass. Professor, PhD, MD, + 46 8 123 70 000, lina.davies.forsman@ki.se
lina.davies.forsman@ki.se
About this study
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:
Read more
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
- 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.
Read the detailed 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.
- Conditions
- Tuberculosis, Pulmonary
- Being tested
- MIPD
- Keywords
- model-informed precision dosing, individualised dosing
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MIPDOther
This is a non-inverventional study
| Study group | Role | What they receive |
|---|---|---|
| Pulmonary tuberculosis | Not described Receives: Other: MIPD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of predicted dose
Proportion of participants with predicted doses of rifampicin, isoniazid and/or pyrazinamide within 5 days from sampling (%)
Measured: Within the first 5 days from sampling
Secondary outcomes (2)
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
Measured: Through study completion, an average of one month
Model precision
Precision of the model comparing predicted drug levels to the detected drug levels (%)
Measured: Through study completion, an average of one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2024
- Study start1 Nov 2025
- Primary completionOct 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Tuberculosis, PulmonaryStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital, Region Östergötland
- Responsible party
- Principal investigator, Lina Davies Forsman, Karolinska Institutet
- Investigators
- Lina Davies Forsman, MD, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06585358
- Sponsor's protocol ID
- 4-1624/2023
- Acronym
- DoseTB
- Status last verified
- Nov 2025
- First submitted
- 13 Jun 2024
- Last updated
- 21 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33708753Azuma 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.
PubMed 23150149Pasipanodya 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.
PubMed 23901086Niward 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.
PubMed 30124844
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT06585358
- Acronym / sponsor ID
- DoseTB / 4-1624/2023
- Conditions
- Tuberculosis, Pulmonary
- Keywords
- model-informed precision dosing, individualised dosing
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Karolinska University Hospital, Region Östergötland
- Study start
- 1 Nov 2025 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 5 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pulmonary tuberculosis | – | Other: MIPD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MIPDThis is a non-inverventional study | Other | Pulmonary tuberculosis |
Primary outcome
Proportion of predicted dose
Time frame: Within the first 5 days from sampling
Proportion of participants with predicted doses of rifampicin, isoniazid and/or pyrazinamide within 5 days from sampling (%)
2 secondary outcomes
Proportion reaching predicted drug exposure
Time frame: Through study completion, an average of one month
Model precision
Time frame: Through study completion, an average of one month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2025.
- Background: PubMed 33708753Abdulla 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.
- Background: PubMed 23150149Azuma 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.
- Background: PubMed 23901086Pasipanodya 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.
- Background: PubMed 30124844Niward 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lina Davies Forsman, MD, PhD principal investigator
Karolinska Institutet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, Pulmonary, run by Karolinska Institutet at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lina Davies Forsman, MD, PhD, Associate Professor (08-12370000, lina.davies.forsman@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of predicted dose (time frame: Within the first 5 days from sampling). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06585358, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2025.