Diagnostics and Pharmacotherapy for Severe Forms of TB (DMID 15-0100)

Major Research Aim: To study novel molecular diagnostics and the pharmacokinetic variability among a spectrum of TB disease states, including severe forms of TB like disseminated TB, TB meningitis and drug resistant TB, among adults and children from multiple international sites.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections

Sex eligibility

All sexes

Study type

Observational

About this study

Aim 1. Measure pharmacokinetics to anti-tuberculosis (TB) medications in severe TB syndromes (including multidrug-resistant TB, pediatric TB, TB sepsis and TB meningitis) from diverse geographies (including Tanzania, Uganda, Bangladesh, and Siberia) and correlate these findings to TB treatment outcome (TB treatment failure: death/ default/ relapse/ further acquired drug resistance).

Aim 2. Decipher mechanisms of pharmacokinetic variability to TB drugs, particularly malabsorption due to concurrent gastrointestinal disease.

Aim 3. Deployment of quantitative susceptibility testing (minimum inhibitory concentration-MIC) and rapid MIC-informed molecular methods (e.g., TaqMan Array Card-TAC) for M. tuberculosis.

In addition to the stated aims, the primary elements of capacity building requisite for this project include the training in and deployment of the fieldable molecular diagnostic platforms, onsite pharmacokinetic monitoring, and a broad strengthening of longitudinal cohort management for clinical research.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patients admitted to one of the study site hospitals with at least ONE of the following:

Clinical suspicion for TB in a child, as defined by NIH Consensus Case Definitions for TB research in children, and started on TB treatment
Clinical suspicion for TB meningitis, as defined by the International TB Meningitis Workshop Consensus Case Definitions for TB Meningitis
Clinical suspicion for TB sepsis, as defined by the Uganda/PRISM-U definitions
Microbiologic evidence of MDR-TB from a respiratory specimen within the past 6 months

Exclusion criteria

Pregnant women-self reported
Patient unable per treating physician discretion to undergo sample collection
Patient or representative/guardian unable to sign written informed consent
Patient unable to return for follow-up or be contacted by phone for follow-up

Treatment and study plan

Primary outcomes

Measure area under the concentration curve (AUC) to anti-tuberculosis (TB) medications relative to TB treatment outcome in severe TB syndromes

Time frame: December 2019

Severe TB syndromes include multidrug-resistant TB, pediatric TB, TB sepsis and TB meningitis from diverse geographies (including Tanzania, Uganda, Bangladesh, and Siberia). The parameter of most importance to cidal activity of anti-TB medications among the cohort is AUC. TB treatment outcome will be defined as death, microbiological failure, relapse or acquired drug resistance, and machine learning algorithms such as classification and regression tree analyses will be used to define AUC threshold for each anti-TB medication predictive of poor TB treatment outcome. Conventional logistic regression will then be used to determine the additive odds for a patient with one of more medications below an algorithm derived threshold being significantly more likely to have a poor TB treatment outcome.

Secondary outcomes

Collect stool in patients undergoing pharmacokinetic testing to measure the environmental enteropathy index

Time frame: December 2019

Stool will be collected in patients with severe TB syndromes undergoing pharmacokinetic testing and assayed for stool biomarkers of malabsorption (environmental enteropathy index) and modeled as a determinant of those with AUC values of one or more anti-TB medications below thresholds predictive of TB treatment outcome.
Collect stool in patients undergoing pharmacokinetic testing to measure the quantitative burden and species distribution of enteric pathogens by the enteric TAC assay- 35 bacterial, viral, parasitic species)

Time frame: December 2019

Stool will be collected in patients with severe TB syndromes undergoing pharmacokinetic testing and assayed for detection of molecular targets of enteric pathogens by TaqMan Array Card (TAC) platform. Enteric pathogen burden (including the effect of multiple pathogens in a single sample) will be modeled as a determinant of those with AUC values of one or more anti-TB medications below thresholds predictive of TB treatment outcome.

Sponsors and collaborators

Lead sponsor

University of Virginia

Other

Collaborators

Haydom Lutheran Hospital
International Centre for Diarrhoeal Disease Research, Bangladesh
Kilimanjaro Christian Medical Centre, Tanzania
Mbarara University of Science and Technology
National Institute of Allergy and Infectious Diseases (NIAID)
Scientific Center for Family Health and Human Reproduction Problems, Russia
University of Florida

Registry information

Official study title

Diagnostics and Pharmacotherapy for Severe Forms of TB

Important dates

Study start: 2016
Primary completion: 2020
Study completion: 2021
First posted: Jun 18, 2018
Registry last updated: Mar 9, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed