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

NCT06585358 | Recruiting

• 1 other identifier: 4-1624/2023
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Tuberculosis, Pulmonary

Keywords

model-informed precision dosing; individualised dosing

Outcome Measures

Primary Outcomes (1)

• Proportion of predicted dose

  Proportion of participants with predicted doses of rifampicin, isoniazid and/or pyrazinamide within 5 days from sampling (%)

  Within the first 5 days from sampling

Secondary Outcomes (2)

• Proportion reaching predicted drug exposure

  Through study completion, an average of one month

• Model precision

  Through study completion, an average of one month

Study Arms (1)

Pulmonary tuberculosis

Other: MIPD

Interventions

MIPD OTHER

This is a non-inverventional study

Pulmonary tuberculosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• TB treatment with intravenous rifampin (including patients treated at an intensive care unit (ICU) or patients with cerebral TB)
• Study participants with extrapulmonary TB without pulmonary TB.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator
• Region Östergötland: collaborator

Study Sites (2)

Linköping University Hospital

Linköping, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, 17177, Sweden

RECRUITING

Related Publications (4)

• 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.

  PMID: 33708753 BACKGROUND

• 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.

  PMID: 23150149 BACKGROUND

• 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.

  PMID: 23901086 BACKGROUND

• 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.

  PMID: 30124844 BACKGROUND

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Lina Davies Forsman, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lina Davies Forsman, MD, PhD, Associate Professor

CONTACT

08-12370000; lina.davies.forsman@ki.se

Katarina Niward, MD, PhD

CONTACT

+46 10 103 00 00; katarina.niward@liu.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: September 5, 2024
• Study Start: November 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)