Clinical trial NCT03559582: Diagnostics and Pharmacotherapy for Severe Forms of TB (DMID 15-0100)
Official title: Diagnostics and Pharmacotherapy for Severe Forms of TB
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Scientific Center for Family Health and Human Reproduction Problems, Russia
name: Kilimanjaro Christian Medical Centre, Tanzania
name: Haydom Lutheran Hospital
name: Mbarara University of Science and Technology
name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: University of Florida
First posted: 2018-06-18
Enrollment: 478
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be recruited by medical officer review of new admissions to the TB hospitals at the study sites- Kibong'oto National TB Hospital (Tanzania), Haydom Lutheran Hospital (Tanzania), Irkutsk Regional Clinical Tuberculosis Hospital (Siberia/Russian Federation), National Institute of Diseases of the Chest Hospital (Bangladesh), ICDDRB Hospital (Bangladesh), Mbarara Regional Referral Hospital (Uganda).

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

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

Exclusion Criteria:

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

Primary outcomes:
measure: Measure area under the concentration curve (AUC) to anti-tuberculosis (TB) medications relative to TB treatment outcome in severe TB syndromes
timeFrame: December 2019
Secondary outcomes:
measure: Collect stool in patients undergoing pharmacokinetic testing to measure the environmental enteropathy index
timeFrame: December 2019
measure: 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)
timeFrame: December 2019
Other outcomes:
Locations:
Study officials:
affiliation: University of Virginia
name: Scott K Heysell, MD
role: PRINCIPAL_INVESTIGATOR
References: