Pharmacokinetics of Drugs Used to Treat Drug Sensitive Tuberculosis in Breastfeeding Mother-infant Pairs

NCT05840809 | Active Not Recruiting

• 1 other identifier: MILK TB
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pregnant or lactating women requiring treatment for drug sensitive-TB will be identified and invited for sampling. If they are pregnant when identified, they will be invited for sampling after delivery. Plasma and breastmilk samples will be obtained pre-dose and at 2, 4, 6, and 8 hours post-dose. If logistics permit (for example living close to the research unit), the participant will be invited for a further sample at 24 hours post-dose. A heelprick sample will also be obtained from their breastfed infants at maternal trough (prior to maternal dose) and at a random timepoint (once per infant) over the 8-hour pharmacokinetic sampling visit in order to characterize concentrations of these drugs over an 8-hour dosing interval. Total concentrations of plasma and breastmilk Isoniazid, Rifampicin, Pyrazinamide and Ethambutol will be determined. If a participant has her first pharmacokinetic profile in the intensive phase of TB treatment (whilst on all four of isoniazid, rifampicin, pyrazinamide and ethambutol), she will be invited for a subsequent sampling day with the same time points when she is on the continuation phase of therapy (rifampicin and isoniazid).

Conditions

Tuberculosis Active; Breastfeeding; Tuberculosis

Keywords

Breastfeeding; Tuberculosis; Pharmacokinetic

Outcome Measures

Primary Outcomes (12)

• Concentration of rifampicin in maternal plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of rifampicin in breastmilk

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of rifampicin in infant plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of isoniazid in maternal plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of isoniazid in breastmilk

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of isoniazid in infant plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of ethambutol in maternal plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of ethambutol in breastmilk

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of ethambutol in infant plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of pyrazinamide in maternal plasma

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of pyrazinamide in breastmilk

  Pharmacokinetic

  0-24 hours after maternal dose

• Concentration of pyrazinamide in infant plasma

  Pharmacokinetic

  0-24 hours after maternal dose

Secondary Outcomes (11)

• Maximum concentration of rifampicin in maternal plasma

  0-24 hours after maternal dose

• Maximum concentration of rifampicin in breastmilk

  0-24 hours after maternal dose

• Maximum concentration of isoniazid in maternal plasma

  0-24 hours after maternal dose

• Maximum concentration of isoniazid in breastmilk

  0-24 hours after maternal dose

• Maximum concentration of ethambutol in maternal plasma

  0-24 hours after maternal dose

Study Arms (1)

Participants

Women who require first-line treatment for drug-sensitive tuberculosis whilst breastfeeding and their babies. This regimen consists of rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months (intensive phase) followed by a further four months of rifampicin and isoniazid (continuation phase)

Drug: First line tuberculosis treatment

Interventions

First line tuberculosis treatment DRUG

This is an observational study - the decision to use first-line tuberculosis treatment will have already been made by the responsible clinician. The study itself does not require any additional intervention.

Participants

Eligibility Criteria

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

Study Population

Breastfeeding women, including those living with HIV, treated for TB will be recruited prospectively from Infectious Diseases clinic (IDI) and IDI Kampala City Council Authority (KCCA) affiliated clinics. The clinics treat pregnant and breast-feeding women infected with TB. We anticipate that 80% of women will be living with HIV. Drug-drug interactions between antiretroviral therapy (ART) and TB drugs could affect the exposure of TB drugs. Data on concomitant medication will be recorded and included as a covariate in the pharmacokinetic analysis. In accordance with national protocol, the infants of mothers diagnosed with TB treatment will receive isoniazid preventive therapy for six months (the duration of the mothers' TB treatment).

You may qualify if:

• A personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Woman is aged 18 years or older
• Receiving treatment for drug sensitive TB
• Pregnant or breastfeeding at enrolment

You may not qualify if:

• Severe maternal or infant illness which in the opinion of the patient's clinician would interfere with her participation in the study.
• Breastfed infant is aged over 12 months

Sponsors & Collaborators

• University of Liverpool: lead
• Makerere University: collaborator

Study Sites (1)

Infectious Diseases Institute

Kampala, 22418, Uganda

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples will be retained until all pharmacokinetic bioanalysis is complete

MeSH Terms

Conditions

Tuberculosis; Breast Feeding

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Feeding Behavior; Behavior

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Catriona Waitt

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: May 3, 2023
• Study Start: January 20, 2022
• Primary Completion: December 20, 2024
• Study Completion: January 29, 2026
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Protocol, SAP and ICF will shortly become available. Anonymised datasets will become available after primary analysis
• Access Criteria: Permissions to access the documents and datasets can be requested via the MILK Zenodo Community.

Locations

UG (1)