TuberculosisNCT02534727
Sputum Pharmacokinetics of TB Drugs and Bacterial Drug Resistance
An observational study of Tuberculosis and Non-Tuberculosis Mycobacteria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
Trial summary
Background: Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Non-Tuberculosis Mycobacteria
- How many people
- 215 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 27 Jan 2016to 31 Dec 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This is a prospective trial of the pharmacokinetics of TB drugs in the sputum and blood of drug susceptible and drug resistant subjects at the Henan Provincial Chest Hospital in Zhengzhou, China and at the NIH Clinical Center in Bethesda, MD. Patients (inpatients or outpatients) being treated for TB (including those with NTM at the NIH CC) were asked to join the study.@@@@@@@@@@@@
Who may be able to join
- At least 18 years of age
- Diagnosis of TB (and/or NTM for NIH clinical center subjects)
- Ongoing signs and/or symptoms of pulmonary TB (and/or NTM at the NIH CC)
- Suspected drug resistance (drug susceptible allowed at the NIH CC)
- Available to provide at least 3 sputa over 2 or more days
- Taking anti-tuberculosis medicines (or NTM meds at NIH CC) during the time sputa are provided
Show all 11Show fewer
- Thought likely to be Mycobacterium culture positive (including NTM infected for the NIH CC) by enrolling physician
- GeneXpert MTB/RIF sputum TBpositive (China subjects only)
- Likely able to produce sputum samples while on study
- Willing to provide blood samples
- Willing to have samples stored
Who cannot join
- Acute liver or kidney disease
- Conditions which compromise the subject s ability to take or absorb oral drugs
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. They will look at how much medicine is in your sputum (what you cough up) compared to how much is in your blood. They will also investigate a new test to quickly figure out what medicines are likely to treat TB effectively.
Read more
Objective:
To determine the relationship between the concentration of TB drugs in plasma and sputum over time.
Eligibility:
People ages 18 and older who have TB or NTM infection that is suspected to be drug resistant. They must be taking TB or NTM medicines.
Design:
Participants will be screened with medical history.
Participants will be in the study for 2 8 days.
Participants will give 3 or more sputum samples over at least 2 different days. They will cough sputum into a cup.
Participants will have blood drawn 4 times a day on 2 different days.
Read the detailed description
This study will support two avenues of research, pharmacokinetics (PK) of drugs used to treat tuberculosis and resistance to those drugs that has been developed by the pathogen. Given the high inter-individual variability in TB drug exposure, therapeutic drug monitoring would be of value to adjust the drug dose in TB patients in order to improve clinical outcome and minimize toxicity. It is not practiced in most settings for reasons associated with costs but also because blood collection is an invasive procedure. Sputum on the other hand is often produced spontaneously and discarded as waste. Drug levels can be measured in sputum just as in plasma. Here we will test the hypothesis that sputum drug levels are predictive of drug concentrations in plasma and/or in specific lesion compartments such as the caseum of open cavities. We will also characterize the exposure of standard 1st and 2nd line TB drugs at one of the sites of infection, since sputum is in direct contact with cavity caseum. The subjects will contribute three or more sputum samples spontaneously produced over at least two days and four blood samples following drug administration on two different days (8 blood samples total). The data will be analyzed using population PK modeling approaches to generate concentration-time profiles and 24-hour area under the curve (AUC) of each study drug in sputum. Correlations between these values, plasma and lesion AUCs will be examined. We will draw from a recently completed TB lesion pharmacokinetic study (www.ClinicalTrials.gov #NCT00816426) to seek correlations between drug exposure in sputum and in pulmonary lesions. In addition to drug concentrations, sputum will be cultured by standard methods to isolate Mycobacterium tuberculosis (Mtb), determine the drug resistance profile, and be saved for testing a second generation of the Xpert TB XDR assay.
- Conditions
- Tuberculosis, Non-Tuberculosis Mycobacteria
- Keywords
- Pharmacokinetic-Moedeling, Tuberculosis, Therapeutic Drug Monitoring, Drug-Levels, Caseum, Natural History
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sputum and blood participants | These participants will contribute both blood and sputum to the study | |
| Sputum only participants | These participants will only contribute sputum to the study |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the AUC (0-24) in sputum and blood.
drug-specific correlation coefficients of the AUCs for sputum and blood
Measured: 0-24 hrs
Secondary outcomes (1)
drug-specific time-concentration curves, as well as drug exposure in sputum relative to that in cavity caseum
Estimation of time-concentration curves, as well as variance components of sputum PK parameters to better inform sputum PK sampling in future studies. Additionally, the relationship between drug-specific exposures in cavity caseum, from historical data, and that in sputum will be evaluated using correlation coefficients.
Measured: Throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2015 (estimated)
- Study start27 Jan 2016
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
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 National Institute of Allergy and Infectious Diseases (NIAID)The 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
- 215 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Clifton E Barry, Ph.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02534727
- Sponsor's protocol ID
- 150187
- Other IDs
- 15-I-0187
- Status last verified
- Mar 2022
- First submitted
- 26 Aug 2015
- Last updated
- 29 Mar 2022
- Results posted
- No
Publications
Wilkins JJ, Savic RM, Karlsson MO, Langdon G, McIlleron H, Pillai G, Smith PJ, Simonsson US. Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Antimicrob Agents Chemother. 2008 Jun;52(6):2138-48. doi: 10.1128/AAC.00461-07. Epub 2008 Apr 7.
PubMed 18391026Dartois V. Drug forgiveness and interpatient pharmacokinetic variability in tuberculosis. J Infect Dis. 2011 Dec 15;204(12):1827-9. doi: 10.1093/infdis/jir662. Epub 2011 Oct 21. No abstract available.
PubMed 22021619Peloquin C. Use of therapeutic drug monitoring in tuberculosis patients. Chest. 2004 Dec;126(6):1722-4. doi: 10.1378/chest.126.6.1722. No abstract available.
PubMed 15596662
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sputum Pharmacokinetics of TB Drugs and Bacterial Drug Resistance
- ClinicalTrials.gov ID
- NCT02534727
- Acronym / sponsor ID
- 150187
- Conditions
- Tuberculosis, Non-Tuberculosis Mycobacteria
- Keywords
- Pharmacokinetic-Moedeling, Tuberculosis, Therapeutic Drug Monitoring, Drug-Levels, Caseum, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 215 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 27 Jan 2016 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 28 Aug 2015 (estimated)
- 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.
Background:
Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. They will look at how much medicine is in your sputum (what you cough up) compared to how much is in your blood. They will also investigate a new test to quickly figure out what medicines are likely to treat TB effectively.
Objective:
To determine the relationship between the concentration of TB drugs in plasma and sputum over time.
Eligibility:
People ages 18 and older who have TB or NTM infection that is suspected to be drug resistant. They must be taking TB or NTM medicines.
Design:
Participants will be screened with medical history.
Participants will be in the study for 2 8 days.
Participants will give 3 or more sputum samples over at least 2 different days. They will cough sputum into a cup.
Participants will have blood drawn 4 times a day on 2 different days.
Detailed description
This study will support two avenues of research, pharmacokinetics (PK) of drugs used to treat tuberculosis and resistance to those drugs that has been developed by the pathogen. Given the high inter-individual variability in TB drug exposure, therapeutic drug monitoring would be of value to adjust the drug dose in TB patients in order to improve clinical outcome and minimize toxicity. It is not practiced in most settings for reasons associated with costs but also because blood collection is an invasive procedure. Sputum on the other hand is often produced spontaneously and discarded as waste. Drug levels can be measured in sputum just as in plasma. Here we will test the hypothesis that sputum drug levels are predictive of drug concentrations in plasma and/or in specific lesion compartments such as the caseum of open cavities. We will also characterize the exposure of standard 1st and 2nd line TB drugs at one of the sites of infection, since sputum is in direct contact with cavity caseum. The subjects will contribute three or more sputum samples spontaneously produced over at least two days and four blood samples following drug administration on two different days (8 blood samples total). The data will be analyzed using population PK modeling approaches to generate concentration-time profiles and 24-hour area under the curve (AUC) of each study drug in sputum. Correlations between these values, plasma and lesion AUCs will be examined. We will draw from a recently completed TB lesion pharmacokinetic study (www.ClinicalTrials.gov #NCT00816426) to seek correlations between drug exposure in sputum and in pulmonary lesions. In addition to drug concentrations, sputum will be cultured by standard methods to isolate Mycobacterium tuberculosis (Mtb), determine the drug resistance profile, and be saved for testing a second generation of the Xpert TB XDR assay.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sputum and blood participants | – | –These participants will contribute both blood and sputum to the study |
| Sputum only participants | – | –These participants will only contribute sputum to the study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This is a prospective trial of the pharmacokinetics of TB drugs in the sputum and blood of drug susceptible and drug resistant subjects at the Henan Provincial Chest Hospital in Zhengzhou, China and at the NIH Clinical Center in Bethesda, MD. Patients (inpatients or outpatients) being treated for TB (including those with NTM at the NIH CC) were asked to join the study.@@@@@@@@@@@@
Key inclusion criteria (11 listed)
Key exclusion criteria (2 listed)
- Acute liver or kidney disease
- Conditions which compromise the subject s ability to take or absorb oral drugs
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
The primary endpoint is the AUC (0-24) in sputum and blood.
Time frame: 0-24 hrs
drug-specific correlation coefficients of the AUCs for sputum and blood
1 secondary outcome
drug-specific time-concentration curves, as well as drug exposure in sputum relative to that in cavity caseum
Time frame: Throughout
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 29 Mar 2022.
- Background: PubMed 18391026Wilkins JJ, Savic RM, Karlsson MO, Langdon G, McIlleron H, Pillai G, Smith PJ, Simonsson US. Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Antimicrob Agents Chemother. 2008 Jun;52(6):2138-48. doi: 10.1128/AAC.00461-07. Epub 2008 Apr 7.
- Background: PubMed 22021619Dartois V. Drug forgiveness and interpatient pharmacokinetic variability in tuberculosis. J Infect Dis. 2011 Dec 15;204(12):1827-9. doi: 10.1093/infdis/jir662. Epub 2011 Oct 21. No abstract available.
- Background: PubMed 15596662Peloquin C. Use of therapeutic drug monitoring in tuberculosis patients. Chest. 2004 Dec;126(6):1722-4. doi: 10.1378/chest.126.6.1722. No abstract available.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Clifton E Barry, Ph.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Non-Tuberculosis Mycobacteria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
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 11 inclusion and 2 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 29 Mar 2022. 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, China. 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?
The primary endpoint is the AUC (0-24) in sputum and blood. (time frame: 0-24 hrs). 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 NCT02534727, 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 29 Mar 2022.