TuberculosisNCT03559582
Diagnostics and Pharmacotherapy for Severe Forms of TB (DMID 15-0100)
An observational study of Tuberculosis, run by University of Virginia.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tuberculosis
- How many people
- 478 participants
- Where
- No sites listed yet
- Study dates
- 28 Apr 2016to 31 Jan 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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).
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: Diagnostics and Pharmacotherapy for Severe Forms of TB
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.
Read the 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.
- Conditions
- Tuberculosis
- Medical subject headings
- Tuberculosis
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: December 2019
Secondary outcomes (2)
Collect stool in patients undergoing pharmacokinetic testing to measure the environmental enteropathy index
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.
Measured: 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)
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.
Measured: December 2019
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2018
- Study start28 Apr 2016
- Primary completion31 Jul 2020
- Study completion31 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 478 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Scientific Center for Family Health and Human Reproduction Problems, Russia, Kilimanjaro Christian Medical Centre, Tanzania, Haydom Lutheran Hospital, Mbarara University of Science and Technology, International Centre for Diarrhoeal Disease Research, Bangladesh, University of Florida
- Responsible party
- Principal investigator, Scott Heysell, MD, University of Virginia
- Investigators
- Scott K Heysell, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03559582
- Sponsor's protocol ID
- 18452
- Other IDs
- U01AI115594
- Status last verified
- Mar 2022
- First submitted
- 22 Feb 2018
- Last updated
- 9 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35731948
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostics and Pharmacotherapy for Severe Forms of TB
- ClinicalTrials.gov ID
- NCT03559582
- Acronym / sponsor ID
- 18452
- Conditions
- Tuberculosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 478 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Scientific Center for Family Health and Human Reproduction Problems, Russia, Kilimanjaro Christian Medical Centre, Tanzania, Haydom Lutheran Hospital, Mbarara University of Science and Technology, International Centre for Diarrhoeal Disease Research, Bangladesh, University of Florida
- Study start
- 28 Apr 2016 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 18 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
2 secondary outcomes
Collect stool in patients undergoing pharmacokinetic testing to measure the environmental enteropathy index
Time frame: 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)
Time frame: December 2019
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2022.
- Derived from this study: PubMed 35731948Heysell 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott K Heysell, MD principal investigator
University of Virginia
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, run by University of Virginia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03559582, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.