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

NCT03559582 | Completed

• 2 other identifiers: 18452U01AI115594
• Study Type: observational
• Target: 478
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

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

  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.

  December 2019

Secondary Outcomes (2)

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

  December 2019

• 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)

  December 2019

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Related Publications (1)

• Heysell SK, Mpagama SG, Ogarkov OB, Conaway M, Ahmed S, Zhdanova S, Pholwat S, Alshaer MH, Chongolo AM, Mujaga B, Sariko M, Saba S, Rahman SMM, Uddin MKM, Suzdalnitsky A, Moiseeva E, Zorkaltseva E, Koshcheyev M, Vitko S, Mmbaga BT, Kibiki GS, Pasipanodya JG, Peloquin CA, Banu S, Houpt ER. Pharmacokinetic-Pharmacodynamic Determinants of Clinical Outcomes for Rifampin-Resistant Tuberculosis: A Multisite Prospective Cohort Study. Clin Infect Dis. 2023 Feb 8;76(3):497-505. doi: 10.1093/cid/ciac511.

  PMID: 35731948 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

This study will use clinical and related phenotypic data and saliva samples to identify and characterize genetic and molecular biological markers that will enrich our understanding of the biological basis of an individual's response to anti-TB drugs.

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Scott K Heysell, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Division of Infectious Diseases and International Health

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: June 18, 2018
• Study Start: April 28, 2016
• Primary Completion: July 31, 2020
• Study Completion: January 31, 2021
• Last Updated: March 9, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share