TuberculosisNCT03625739
Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
An observational study of Tuberculosis, run by Beijing Children's Hospital at 1 site in China.
Trial summary
This study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- anti-tuberculosis drug
- How many people
- 800 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2018to 31 Dec 2026
- How long will I take part?
- 18 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 1 day to 18 years
- All sexes
- Child, Adult
Study population: Children with anti-tuberculosis therapies.
Who may be able to join
- Children (0-18 years old) with anti-tuberculosis therapy against TB.
- The anti-tuberculsis therapy includes drugs commonly used in children infectious diseases
- Informed consent signed by the parents and/or guardians.
Who cannot join
- Anti-tuberculosis drugs aren't involved in the therapies of children.
- It is unable to provide complete medical records or the current condition cannot accept the study process.
- Patients are allergic to anti-tuberculsis drugs.
- Parents and/or guardians do not agree to participate in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Beijing Children's Hospital of Capital Medical University
Beijing
Adong Shen, Master, 13370115087, shenad16@hotmail.com
About this study
This study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. In this study, the investigators will detect drug concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of anti-tuberculsis drugs with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of TB in children. It will also set the foundation for further studies to improve anti-tuberculosis drug therapies for children.
Read the detailed description
1.Establish population pharmacokinetic (PPK) models of each anti-tuberculsis drug in children by nonlinear mixed effect modeling (NONMEM).
- At different timepoint after anti-tuberculsis drug administration, plasma samples of 100 children will be collected from neonatal intensive care unit (NICU) and pneumology department for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of anti-tuberculsis drug will be established by NONMEM program.
- The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).
2.Evaluation of the clinical feasibility and safety of individualized dosing.
- According the results of PPK models, the investigators will use dosages recommended in models to cure TB children in prospective studies. For anti-tuberculsis drug, 50 children will be collected.
- The investigators will compare the therapeutic effects and safety between children with conventional therapies and children with individualized therapies, including proportions of children with effective drug concentration, improvement speed of of children, liver and kidney functions of of children, adverse reactions of drugs and so on.
- Conditions
- Tuberculosis
- Being tested
- anti-tuberculosis drug
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-tuberculosis drugDrug
Also called Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
The intervention drugs are prescribed by treating caregiver
What is being measured
The primary outcome is the main question the study is designed to answer.
maximum concentration (Cmax)
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum
Measured: up to 4 weeks
Secondary outcomes (4)
time to achieve maximum concentration (Tmax)
Tmax is the term used in pharmacokinetics to describe the time at which the Cmax
Measured: up to 4 weeks
absorption rate constant (ka)
Ka is the rate constant of drug absorption.
Measured: up to 4 weeks
elimination rate constant (kel)
The elimination rate constant is a value used in pharmacokinetics to describe the rate at which a drug is removed from the system.
Measured: up to 4 weeks
half-life (t1/2)
Half-life is the time required for a quantity to reduce to half its initial value.
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start1 Jul 2018
- Primary completion1 Oct 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
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.
- 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
- 800 participants (estimated)
- Target duration
- 18 Years
Sponsor and investigators
- Lead sponsor
- Beijing Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong University, Hopital Universitaire Robert-Debre, Rennes University Hospital
- Responsible party
- Principal investigator, Adong Shen, Beijing Children's Hospital
- Investigators
- A-Dong Shen, Master, Principal investigator, Beijing Children's Hospital of Capital Medical UniversityYu-Jie Qi, Master, Study director, Beijing Children's Hospital of Capital Medical UniversityWei Zhao, Doctor, Study director, Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03625739
- Sponsor's protocol ID
- BCH_PPK003
- Status last verified
- Aug 2018
- First submitted
- 8 Aug 2018
- Last updated
- 15 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4.
PubMed 26289222Ho PL, Lo PY, Chow KH, Lau EH, Lai EL, Cheng VC, Kao RY. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect. 2010 Feb;60(2):140-5. doi: 10.1016/j.jinf.2009.11.011. Epub 2009 Dec 2.
PubMed 19961873Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. doi: 10.1056/NEJMra035092. No abstract available.
PubMed 13679531
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Anti-tuberculosis Drugs in Children With Tuberculosis
- ClinicalTrials.gov ID
- NCT03625739
- Acronym / sponsor ID
- BCH_PPK003
- Conditions
- Tuberculosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Beijing Children's HospitalUniversity, hospital or other
- Collaborators
- Shandong University, Hopital Universitaire Robert-Debre, Rennes University Hospital
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 10 Aug 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.
This study is based on the hypothesis that the pharmacokinetics of anti-tuberculosis drugs in TB children are different from adults. The investigators aim to study the population pharmacokinetics of children receiving the anti-tuberculsis drugs for treatment of TB. In this study, the investigators will detect drug concentration in plasma by using residual blood samples of blood gas analysis and other clinical tests and employ computers for constructing population pharmacokinetic models. In addition, the investigators also want to correlate use of anti-tuberculsis drugs with treatment effectiveness and incidence of adverse effects in children. This novel knowledge will allow better and more rational approaches to the treatment of TB in children. It will also set the foundation for further studies to improve anti-tuberculosis drug therapies for children.
Detailed description
1.Establish population pharmacokinetic (PPK) models of each anti-tuberculsis drug in children by nonlinear mixed effect modeling (NONMEM).
- At different timepoint after anti-tuberculsis drug administration, plasma samples of 100 children will be collected from neonatal intensive care unit (NICU) and pneumology department for each drug. The clinical information includes demography, medication, concentration data, blood biochemical parameters and so on .
- Plasma samples will be tested by high performance liquid chromatography (HPLC).
- PPK models of anti-tuberculsis drug will be established by NONMEM program.
- The reliability and stability of the PPK model will be evaluated by 1000 times of Bootstrap procedure and normalized predictive distribution error (NPDE).
2.Evaluation of the clinical feasibility and safety of individualized dosing.
- According the results of PPK models, the investigators will use dosages recommended in models to cure TB children in prospective studies. For anti-tuberculsis drug, 50 children will be collected.
- The investigators will compare the therapeutic effects and safety between children with conventional therapies and children with individualized therapies, including proportions of children with effective drug concentration, improvement speed of of children, liver and kidney functions of of children, adverse reactions of drugs and so on.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 18 Years
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Age groups
- Child, Adult
- Study population
- Children with anti-tuberculosis therapies.
Key inclusion criteria (3 listed)
- Children (0-18 years old) with anti-tuberculosis therapy against TB.
- The anti-tuberculsis therapy includes drugs commonly used in children infectious diseases
- Informed consent signed by the parents and/or guardians.
Key exclusion criteria (4 listed)
- Anti-tuberculosis drugs aren't involved in the therapies of children.
- It is unable to provide complete medical records or the current condition cannot accept the study process.
- Patients are allergic to anti-tuberculsis drugs.
- Parents and/or guardians do not agree to participate in this study.
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 |
|---|---|---|
| anti-tuberculosis drugAlso: Isoniazid, Rifampicin, Pyrazinamide, EthambutolThe intervention drugs are prescribed by treating caregiver | Drug | – |
Primary outcome
maximum concentration (Cmax)
Time frame: up to 4 weeks
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum
4 secondary outcomes
time to achieve maximum concentration (Tmax)
Time frame: up to 4 weeks
absorption rate constant (ka)
Time frame: up to 4 weeks
elimination rate constant (kel)
Time frame: up to 4 weeks
half-life (t1/2)
Time frame: up to 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- Background: PubMed 26289222Jacqz-Aigrain E, Leroux S, Zhao W, van den Anker JN, Sharland M. How to use vancomycin optimally in neonates: remaining questions. Expert Rev Clin Pharmacol. 2015;8(5):635-48. doi: 10.1586/17512433.2015.1060124. Epub 2015 Aug 4.
- Background: PubMed 19961873Ho PL, Lo PY, Chow KH, Lau EH, Lai EL, Cheng VC, Kao RY. Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong. J Infect. 2010 Feb;60(2):140-5. doi: 10.1016/j.jinf.2009.11.011. Epub 2009 Dec 2.
- Background: PubMed 13679531Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. doi: 10.1056/NEJMra035092. No abstract available.
- Individual participant dataSharing planned: Yes
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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.
A-Dong Shen, Master principal investigator
Beijing Children's Hospital of Capital Medical University
Yu-Jie Qi, Master study director
Beijing Children's Hospital of Capital Medical University
Wei Zhao, Doctor study director
Children's Hospital of Hebei Province;Shandong Provincial Qianfoshan Hospital
1 site 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 Beijing Children's Hospital at 1 site in China.
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 3 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: looking for participants now, as of the sponsor's last update on 15 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact A-Dong Shen, Master (+86-010-59616898, shenad16@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
maximum concentration (Cmax) (time frame: up to 4 weeks). 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 NCT03625739, 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 15 Aug 2018.