TuberculosisPEE-TBNCT05283967
Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
An observational study of Tuberculosis, run by University of Virginia at 2 sites in United States.
Trial summary
The purpose of the study is to generate receiver-operating-characteristic (ROC) curves for urine colorimetry to identify tuberculosis (TB) patients (children and adults) with low drug anti-TB drug exposures, which will define the diagnostic accuracy. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- urine colorimetric assay
- How many people
- 150 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2019to 1 Dec 2023
- 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study personnel will review the daily clinic rosters at each enrollment site to identify patients with TB who have initiated or are planning to initiate first-line anti-TB therapy with a regimen that includes isoniazid, rifampin, and pyrazinamide.
Who may be able to join
- Patients of male and female sex meeting all of these criteria:
- Those 4 years and older;
- Diagnosed with active TB and initiation of combination anti-TB therapy with isoniazid, rifampin, and pyrazinamide, with or without DM;
- Able to provide informed consent and assent for those 7-17 years old.
Who cannot join
- Anuric (i.e. not capable of producing urine due to chronic renal disease);
- Pregnancy or breastfeeding;
- Prisoners
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Virginia
Charlottesville, Virginia, 22908
Rutgers, The State University of New Jersey
Newark, New Jersey, 07103
About this study
The purpose of the study is to generate receiver-operating-characteristic (ROC) curves for urine colorimetry to identify tuberculosis (TB) patients (children and adults) with low drug anti-TB drug exposures, which will define the diagnostic accuracy. The central hypothesis is that urine colorimetry will successfully identify patients with low anti-TB serum drug levels, and do so with diagnostic characteristics similar to other widely used tests in TB management.
Read the detailed description
TB remains a leading infectious disease cause-of-death worldwide, with an estimated 1.5 million TB deaths each year. There is wide variability in absorption and metabolism of the anti-TB drugs, and low drug concentrations in blood are associated with inferior TB treatment outcomes, including treatment failure, relapse, and the emergence of drug-resistant infections. According to the most recent CDC/ATS/IDSA guidelines for TB treatment, therapeutic drug monitoring should be routinely considered for use among patients in high-risk groups, including adults with co-morbid type 2 diabetes mellitus (DM) and children. However, therapeutic drug monitoring requires sophisticated laboratory techniques unavailable for millions of patients receiving TB therapy in resource-limited settings where the vast majority of TB cases are treated. A new approach to measuring anti-TB drug exposures, based on technology easily adapted to resource-limited settings, is vitally needed and would be in line the World Health Organization's goal of the optimization of anti-TB drug regimens as a key component of the End TB Strategy.
A simple, inexpensive test to identify pediatric and adult TB patients with low drug exposures, available at the point-of-care at the time of the patient encounter, would support clinical decision-making. The performance of therapeutic drug monitoring requires specialty laboratory capabilities, such as high-performance liquid chromatography or gas chromatography. Technical expertise is also required to collect, process, and ship samples to the specialty laboratory. In many high-burden settings, the complexity and cost of these laboratory methods preclude the use of therapeutic drug monitoring in the clinical care of tuberculosis patients. These complexities also foster a dependence of TB endemic sites on laboratories in resource-rich environments. Consequently, patients with inadequate drug exposures cannot be identified early in anti-TB therapy, at the critical time when dosing adjustments could be expected to improve treatment outcomes.
Urine colorimetry provides a low-technology approach for measuring anti-TB drug exposures, suitable for point-of-care testing. Colorimetry is the measurement of intensity of signal at a specific wavelength in the visible region of the spectrum. Urine colorimetry was evaluated as a method to assess the relative bioavailability of different fixed-dose combinations of anti-TB drugs administered to healthy volunteers. The study is based on the scientific premise that more detailed anti-TB drug exposure information can be obtained from urine sampling during TB treatment, not only to determine the presence or absence of drugs or metabolites, but to determine whether the presence of drugs or metabolites has surpassed a critical exposure threshold, informing drug dosing decision-making at the point-of-care. Potential advantages of urine colorimetric methods include a non-invasive sampling approach, improved patient acceptability, and the low cost and stability of chemical reagents. Colorimetry is particularly suited for point-of-care diagnostics, possibly with battery-operated or smartphone-based tools. With a simple diagnostic test available at the point-of-care, with results provided at the time of the clinical encounter, the TB clinician will be able to adjust drug doses and optimize regimens.
- Conditions
- Tuberculosis
- Being tested
- urine colorimetric assay
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
urine colorimetric assayDiagnostic test
Colorimetric assays will be performed for urine drug concentrations of rifampin, isoniazid and pyrazinamide from urine collected throughout one dosing interval. Assay results will experimental only and not used to change patient care.
| Study group | Role | What they receive |
|---|---|---|
| Adults and children, U.S. | A prospective, observational study of the pharmacokinetics of first-line anti-TB drugs (isoniazid, rifampin, and pyrazinamide) among TB patients (i.e. patients with active TB disease) will be conducted. Receives: Diagnostic Test: urine colorimetric assay | |
| Tanzanian children | A prospective, observational study of the pharmacokinetics of first-line anti-TB drugs (isoniazid, rifampin, and pyrazinamide) among TB patients (i.e. patients with active TB disease) will be conducted. Receives: Diagnostic Test: urine colorimetric assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine Cmax
Urine peak concentration (Cmax) of rifampin as determined by urine colorimetry
Measured: Day 1
Urine rifampin AUC
Urine total rifampin area under the concentration time curve (AUC) as determined by urine colorimetry
Measured: Day 1
Urine isoniazid Cmax
Urine peak concentration (Cmax) of isoniazid as determined by urine colorimetry
Measured: Day 1
Urine isoniazid AUC
Urine total isoniazid area under the concentration time curve as determined by urine colorimetry
Measured: Day 1
Urine pyrazinamide Cmax
Urine peak concentration (Cmax) of pyrazinamide as determined by urine colorimetry
Measured: Day 1
Urine pyrazinamide AUC
Urine total pyrazinamide area under the concentration time curve as determined by urine colorimetry
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2022
- Study start1 Jan 2019
- Primary completion30 Dec 2022
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott Heysell, MD, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05283967
- Sponsor's protocol ID
- 20944
- Acronym
- PEE-TB
- Status last verified
- May 2024
- First submitted
- 8 Mar 2022
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: All study participant data will be maintained in a de-identified dataset. At study conclusion, investigators will determined plan for IPD sharing.
Publications
Szipszky C, Van Aartsen D, Criddle S, Rao P, Zentner I, Justine M, Mduma E, Mpagama S, Al-Shaer MH, Peloquin C, Thomas TA, Vinnard C, Heysell SK. Determination of Rifampin Concentrations by Urine Colorimetry and Mobile Phone Readout for Personalized Dosing in Tuberculosis Treatment. J Pediatric Infect Dis Soc. 2021 Mar 26;10(2):104-111. doi: 10.1093/jpids/piaa024.
PubMed 32170944Zentner I, Modongo C, Zetola NM, Pasipanodya JG, Srivastava S, Heysell SK, Mpagama S, Schlect HP, Gumbo T, Bisson GP, Vinnard C. Urine colorimetry for therapeutic drug monitoring of pyrazinamide during tuberculosis treatment. Int J Infect Dis. 2018 Mar;68:18-23. doi: 10.1016/j.ijid.2017.12.017. Epub 2017 Dec 15.
PubMed 29253711Petros de Guex K, Augustino D, Mejan P, Gadiye R, Massong C, Lukumay S, Msoka P, Sariko M, Kimathi D, Vinnard C, Xie Y, Mmbaga B, Pfaeffle H, Geba M, Heysell SK, Mduma E, Thomas TA. Roadblocks and resilience: A qualitative study of the impact of pediatric tuberculosis on Tanzanian households and solutions from caregivers. Glob Public Health. 2023 Jan;18(1):2196569. doi: 10.1080/17441692.2023.2196569.
PubMed 37021699
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urine Colorimetry for Tuberculosis Pharmacokinetics Evaluation in Children and Adults
- ClinicalTrials.gov ID
- NCT05283967
- Acronym / sponsor ID
- PEE-TB / 20944
- Conditions
- Tuberculosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Rutgers, The State University of New Jersey, University of Florida
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 17 Mar 2022 (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.
The purpose of the study is to generate receiver-operating-characteristic (ROC) curves for urine colorimetry to identify tuberculosis (TB) patients (children and adults) with low drug anti-TB drug exposures, which will define the diagnostic accuracy. The central hypothesis is that urine colorimetry will successfully identify patients with low anti-TB serum drug levels, and do so with diagnostic characteristics similar to other widely used tests in TB management.
Detailed description
TB remains a leading infectious disease cause-of-death worldwide, with an estimated 1.5 million TB deaths each year. There is wide variability in absorption and metabolism of the anti-TB drugs, and low drug concentrations in blood are associated with inferior TB treatment outcomes, including treatment failure, relapse, and the emergence of drug-resistant infections. According to the most recent CDC/ATS/IDSA guidelines for TB treatment, therapeutic drug monitoring should be routinely considered for use among patients in high-risk groups, including adults with co-morbid type 2 diabetes mellitus (DM) and children. However, therapeutic drug monitoring requires sophisticated laboratory techniques unavailable for millions of patients receiving TB therapy in resource-limited settings where the vast majority of TB cases are treated. A new approach to measuring anti-TB drug exposures, based on technology easily adapted to resource-limited settings, is vitally needed and would be in line the World Health Organization's goal of the optimization of anti-TB drug regimens as a key component of the End TB Strategy.
A simple, inexpensive test to identify pediatric and adult TB patients with low drug exposures, available at the point-of-care at the time of the patient encounter, would support clinical decision-making. The performance of therapeutic drug monitoring requires specialty laboratory capabilities, such as high-performance liquid chromatography or gas chromatography. Technical expertise is also required to collect, process, and ship samples to the specialty laboratory. In many high-burden settings, the complexity and cost of these laboratory methods preclude the use of therapeutic drug monitoring in the clinical care of tuberculosis patients. These complexities also foster a dependence of TB endemic sites on laboratories in resource-rich environments. Consequently, patients with inadequate drug exposures cannot be identified early in anti-TB therapy, at the critical time when dosing adjustments could be expected to improve treatment outcomes.
Urine colorimetry provides a low-technology approach for measuring anti-TB drug exposures, suitable for point-of-care testing. Colorimetry is the measurement of intensity of signal at a specific wavelength in the visible region of the spectrum. Urine colorimetry was evaluated as a method to assess the relative bioavailability of different fixed-dose combinations of anti-TB drugs administered to healthy volunteers. The study is based on the scientific premise that more detailed anti-TB drug exposure information can be obtained from urine sampling during TB treatment, not only to determine the presence or absence of drugs or metabolites, but to determine whether the presence of drugs or metabolites has surpassed a critical exposure threshold, informing drug dosing decision-making at the point-of-care. Potential advantages of urine colorimetric methods include a non-invasive sampling approach, improved patient acceptability, and the low cost and stability of chemical reagents. Colorimetry is particularly suited for point-of-care diagnostics, possibly with battery-operated or smartphone-based tools. With a simple diagnostic test available at the point-of-care, with results provided at the time of the clinical encounter, the TB clinician will be able to adjust drug doses and optimize regimens.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adults and children, U.S. | – | Diagnostic Test: urine colorimetric assayA prospective, observational study of the pharmacokinetics of first-line anti-TB drugs (isoniazid, rifampin, and pyrazinamide) among TB patients (i.e. patients with active TB disease) will be conducted. |
| Tanzanian children | – | Diagnostic Test: urine colorimetric assayA prospective, observational study of the pharmacokinetics of first-line anti-TB drugs (isoniazid, rifampin, and pyrazinamide) among TB patients (i.e. patients with active TB disease) will be conducted. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study personnel will review the daily clinic rosters at each enrollment site to identify patients with TB who have initiated or are planning to initiate first-line anti-TB therapy with a regimen that includes isoniazid, rifampin, and pyrazinamide.
Key inclusion criteria (4 listed)
- Those 4 years and older;
- Diagnosed with active TB and initiation of combination anti-TB therapy with isoniazid, rifampin, and pyrazinamide, with or without DM;
- Able to provide informed consent and assent for those 7-17 years old.
Key exclusion criteria (3 listed)
- Anuric (i.e. not capable of producing urine due to chronic renal disease);
- Pregnancy or breastfeeding;
- Prisoners
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| urine colorimetric assayColorimetric assays will be performed for urine drug concentrations of rifampin, isoniazid and pyrazinamide from urine collected throughout one dosing interval. Assay results will experimental only and not used to change patient care. | Diagnostic test | Adults and children, U.S., Tanzanian children |
Primary outcome
Urine Cmax
Time frame: Day 1
Urine peak concentration (Cmax) of rifampin as determined by urine colorimetry
Urine rifampin AUC
Time frame: Day 1
Urine total rifampin area under the concentration time curve (AUC) as determined by urine colorimetry
Urine isoniazid Cmax
Time frame: Day 1
Urine peak concentration (Cmax) of isoniazid as determined by urine colorimetry
Urine isoniazid AUC
Time frame: Day 1
Urine total isoniazid area under the concentration time curve as determined by urine colorimetry
Urine pyrazinamide Cmax
Time frame: Day 1
Urine peak concentration (Cmax) of pyrazinamide as determined by urine colorimetry
Urine pyrazinamide AUC
Time frame: Day 1
Urine total pyrazinamide area under the concentration time curve as determined by urine colorimetry
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 8 May 2024.
- Background: PubMed 32170944Szipszky C, Van Aartsen D, Criddle S, Rao P, Zentner I, Justine M, Mduma E, Mpagama S, Al-Shaer MH, Peloquin C, Thomas TA, Vinnard C, Heysell SK. Determination of Rifampin Concentrations by Urine Colorimetry and Mobile Phone Readout for Personalized Dosing in Tuberculosis Treatment. J Pediatric Infect Dis Soc. 2021 Mar 26;10(2):104-111. doi: 10.1093/jpids/piaa024.
- Background: PubMed 29253711Zentner I, Modongo C, Zetola NM, Pasipanodya JG, Srivastava S, Heysell SK, Mpagama S, Schlect HP, Gumbo T, Bisson GP, Vinnard C. Urine colorimetry for therapeutic drug monitoring of pyrazinamide during tuberculosis treatment. Int J Infect Dis. 2018 Mar;68:18-23. doi: 10.1016/j.ijid.2017.12.017. Epub 2017 Dec 15.
- Derived from this study: PubMed 37021699Petros de Guex K, Augustino D, Mejan P, Gadiye R, Massong C, Lukumay S, Msoka P, Sariko M, Kimathi D, Vinnard C, Xie Y, Mmbaga B, Pfaeffle H, Geba M, Heysell SK, Mduma E, Thomas TA. Roadblocks and resilience: A qualitative study of the impact of pediatric tuberculosis on Tanzanian households and solutions from caregivers. Glob Public Health. 2023 Jan;18(1):2196569. doi: 10.1080/17441692.2023.2196569.
- Individual participant dataSharing planned: Undecided. All study participant data will be maintained in a de-identified dataset. At study conclusion, investigators will determined plan for IPD sharing.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, run by University of Virginia at 2 sites in United States.
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 4 inclusion and 3 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 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Urine Cmax (time frame: Day 1). The study lists 6 primary outcomes in all. 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 NCT05283967, which also lists 3 linked publications.
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 8 May 2024.