TuberculosisNCT03800381
Adequacy of the New Pediatric Isoniazid/Rifampin/Pyrazinamide (HRZ) Tablet
An observational study of Tuberculosis and Human Immunodeficiency Virus, run by University of Florida at 1 site in Ghana.
Trial summary
Lack of quality-assured pediatric formulations of the first-line antituberculosis (anti-TB) drugs is barrier to optimized tuberculosis (TB) treatment outcome in children. In 2010 and subsequently modified in 2014, the World Health Organization (WHO) recommended increased dosages of the first-line anti-TB drugs for… Read more about this study
- Who is it for?
- Ages 3 months to 14 years
- Conditions the study is for
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- What is being tested?
- Observational PK study
- Type of treatment
- Pill or oral medicine
- How many people
- 92 participants
- Where
- 1 siteGhana
- Study dates
- 28 Jan 2019to 31 Aug 2024
- 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 3 months to 14 years
- All sexes
- No healthy volunteers
- Child
Study population: Children aged 3 months to14 years with active TB with or without HIV co-infection
Who may be able to join
- Children with active TB with or without HIV coinfection. Active TB diagnosis defined by clinical criteria consistent with active TB and/or a positive AFB smear.
- Available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling.
Who cannot join
- Children with concurrent conditions other than HIV, have acute hepatitis within 30 days of study entry, persistent vomiting, and diarrhea will be excluded from the study.
- Unable to obtain informed signed consent from parent(s) or legal guardian.
- Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea.
- Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
Lack of quality-assured pediatric formulations of the first-line antituberculosis (anti-TB) drugs is barrier to optimized tuberculosis (TB) treatment outcome in children. In 2010 and subsequently modified in 2014, the World Health Organization (WHO) recommended increased dosages of the first-line anti-TB drugs for children, but there were no child-friendly fixed-dose combination (FDC) formulations based on the guidelines. A large proportion of children treated with the new guidelines using old formulations did not achieve the desired rifampin peak concentration (Cmax) > 8 mg/L and pyrazinamide Cmax > 35 mg/L. The TB Alliance and the WHO led the development of a new child-appropriate isoniazid/rifampin/pyrazinamide (HRZ) and isoniazid/rifampin (HR) FDC formulation in line with current WHO recommended dosing guidelines. The new formulations dissolve quickly in liquid, have palatable fruit flavors, and are expected to improved daily adherence but no studies have evaluated the pharmacokinetics (PK) of the FDC formulation in children. The study team hypothesize that the new dispersible HRZ FDC tablet, dosed according to current WHO weight-band dosing recommendations will result in better PK parameters for each drug component than that achieved by the old formulation.
Read the detailed description
This study will evaluate the PK of the new pediatric HRZ FDC tablet in Ghanaian children with TB with and without HIV coinfection. The new HRZ FDC dispersible tablet was designed to be child-friendly and to achieve recommended dosages for each weight-band. The formulation has been rolled out in Africa without PK studies in the target population to verify that the tablets achieves adequate drug concentrations. The current study will evaluate the adequacy of the formulation by examining the PK of the component drugs as well as the effect of HIV coinfection. The direct PK data will be used in a population PK model and stimulations to define optimal weight-band dosages and proportions of the components of the pediatric FDC tablets.
- Conditions
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- Being tested
- Observational PK study
- Keywords
- Pharmacokinetic, Pharmacogenomic, Antituberculosis drugs, Children, Tuberculosis, TB/HIV coinfection
- Medical subject headings
- Tuberculosis, Acquired Immunodeficiency Syndrome, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational PK studyOther
Also called New pediatric isoniazid/rifampin/pyrazinamide (HRZ) FDC tablet
The study team will examine the PK and tolerability of the new HRZ 50/75/150 mg dispersible tablet in children with TB with and without HIV coinfection. Intensive PK testing will be performed after at least 4 weeks of treatment in children on first-line anti-TB therapy using the new pediatric HRZ FDC tablet.
| Study group | Role | What they receive |
|---|---|---|
| Active TB only | Children with clinical diagnosis or acid-fast bacilli (AFB) smear positive TB disease Receives: Other: Observational PK study | |
| Active TB with HIV Co-infection | Children with clinical diagnosis or AFB smear positive TB disease who test positive for HIV infection Receives: Other: Observational PK study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak concentration (Cmax) of isoniazid, rifampin and pyrazinamide in the new pediatric HRZ FDC tablet.
Mean and median Cmax of rifampin, isoniazid and pyrazinamide in children with TB treated with the new HRZ FDC tablet.
Measured: After at least 4 weeks of anti-TB therapy
Area under the time-concentration curve from 0-8 hours (AUC0-8h) of isoniazid, rifampin and pyrazinamide in the new pediatric HRZ FDC tablet.
Mean and median AUC0-8h of rifampin, isoniazid and pyrazinamide in children with TB treated with the new HRZ FDC tablet.
Measured: After at least 4 weeks of anti-TB therapy
Cmax of isoniazid, rifampin and pyrazinamide in children with TB with and without HIV coinfection
Geometric mean values of Cmax of rifampin, isoniazid and pyrazinamide in children with HIV/TB coinfection compared to those with TB alone.
Measured: After at least 4 weeks of anti-TB therapy
AUC0-8h of isoniazid, rifampin and pyrazinamide in children with TB with and without HIV coinfection.
Geometric mean values of AUC0-8h of rifampin, isoniazid and pyrazinamide in children with HIV/TB coinfection compared to those with TB alone.
Measured: After at least 4 weeks of anti-TB therapy
Secondary outcomes (4)
AUC0-8h of isoniazid, rifampin and pyrazinamide in the new versus old pediatric HRZ FDC tablet.
Geometric mean values of AUC0-8h of rifampin, isoniazid, and pyrazinamide in children with TB treated with the new FDC tablet compared to those treated with the old formulation in our previous study (historical controls).
Measured: After at least 4 weeks of anti-TB therapy
Cmax of isoniazid, rifampin and pyrazinamide in the new versus old pediatric HRZ FDC tablet.
Geometric mean values of Cmax of rifampin, isoniazid, and pyrazinamide in children with TB treated with the new FDC tablet compared to those treated with the old formulation in our previous study (historical controls).
Measured: After at least 4 weeks of anti-TB therapy
Proportion of children treated with new pediatric HRZ FDC tablet who develop with liver enzymes elevations.
Frequency of liver enzymes elevations compared to baseline requiring treatment modification in children with TB with and without HIV coinfection.
Measured: After at least 4 weeks of anti-TB therapy
Identify optimal weight-band dosages of the new HRZ FDC tablet
Use a population PK model that incorporates demographic, clinical and genetic factors and stimulations to identify the optimal weight-band dosing of the new FDC formulation.
Measured: After at least 4 weeks of anti-TB therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start28 Jan 2019
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Awewura Kwara, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03800381
- Sponsor's protocol ID
- IRB201801820 - HRZ PK -N
- Other IDs
- 5R01HD071779-11
- Status last verified
- Nov 2024
- First submitted
- 3 Jan 2019
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
- ClinicalTrials.gov ID
- NCT03800381
- Acronym / sponsor ID
- IRB201801820 - HRZ PK -N
- Conditions
- Tuberculosis, Human Immunodeficiency Virus, Coinfection
- Keywords
- Pharmacokinetic, Pharmacogenomic, Antituberculosis drugs, Children, Tuberculosis, TB/HIV coinfection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 28 Jan 2019 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 11 Jan 2019 (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.
Lack of quality-assured pediatric formulations of the first-line antituberculosis (anti-TB) drugs is barrier to optimized tuberculosis (TB) treatment outcome in children. In 2010 and subsequently modified in 2014, the World Health Organization (WHO) recommended increased dosages of the first-line anti-TB drugs for children, but there were no child-friendly fixed-dose combination (FDC) formulations based on the guidelines. A large proportion of children treated with the new guidelines using old formulations did not achieve the desired rifampin peak concentration (Cmax) > 8 mg/L and pyrazinamide Cmax > 35 mg/L. The TB Alliance and the WHO led the development of a new child-appropriate isoniazid/rifampin/pyrazinamide (HRZ) and isoniazid/rifampin (HR) FDC formulation in line with current WHO recommended dosing guidelines. The new formulations dissolve quickly in liquid, have palatable fruit flavors, and are expected to improved daily adherence but no studies have evaluated the pharmacokinetics (PK) of the FDC formulation in children. The study team hypothesize that the new dispersible HRZ FDC tablet, dosed according to current WHO weight-band dosing recommendations will result in better PK parameters for each drug component than that achieved by the old formulation.
Detailed description
This study will evaluate the PK of the new pediatric HRZ FDC tablet in Ghanaian children with TB with and without HIV coinfection. The new HRZ FDC dispersible tablet was designed to be child-friendly and to achieve recommended dosages for each weight-band. The formulation has been rolled out in Africa without PK studies in the target population to verify that the tablets achieves adequate drug concentrations. The current study will evaluate the adequacy of the formulation by examining the PK of the component drugs as well as the effect of HIV coinfection. The direct PK data will be used in a population PK model and stimulations to define optimal weight-band dosages and proportions of the components of the pediatric FDC tablets.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active TB only | – | Other: Observational PK studyChildren with clinical diagnosis or acid-fast bacilli (AFB) smear positive TB disease |
| Active TB with HIV Co-infection | – | Other: Observational PK studyChildren with clinical diagnosis or AFB smear positive TB disease who test positive for HIV infection |
Who may qualify
- Ages
- 3 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Children aged 3 months to14 years with active TB with or without HIV co-infection
Key inclusion criteria (2 listed)
- Children with active TB with or without HIV coinfection. Active TB diagnosis defined by clinical criteria consistent with active TB and/or a positive AFB smear.
- Available for follow-up until completion of TB treatment and/or achievement of a study endpoint like discontinuation of therapy, and/or pharmacokinetic sampling.
Key exclusion criteria (4 listed)
- Children with concurrent conditions other than HIV, have acute hepatitis within 30 days of study entry, persistent vomiting, and diarrhea will be excluded from the study.
- Unable to obtain informed signed consent from parent(s) or legal guardian.
- Have AIDS-related opportunistic infections other than TB, history of or proven acute hepatitis within 30 days of study entry, persistent vomiting, or diarrhea.
- Hemoglobin < 6 g/dl, white blood cells < 2500/mm3, serum creatinine > 1.5 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) > 2 times upper limit of normal.
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 |
|---|---|---|
| Observational PK studyAlso: New pediatric isoniazid/rifampin/pyrazinamide (HRZ) FDC tabletThe study team will examine the PK and tolerability of the new HRZ 50/75/150 mg dispersible tablet in children with TB with and without HIV coinfection. Intensive PK testing will be performed after at least 4 weeks of treatment in children on first-line anti-TB therapy using the new pediatric HRZ FDC tablet. | Other | Active TB only, Active TB with HIV Co-infection |
Primary outcome
Peak concentration (Cmax) of isoniazid, rifampin and pyrazinamide in the new pediatric HRZ FDC tablet.
Time frame: After at least 4 weeks of anti-TB therapy
Mean and median Cmax of rifampin, isoniazid and pyrazinamide in children with TB treated with the new HRZ FDC tablet.
Area under the time-concentration curve from 0-8 hours (AUC0-8h) of isoniazid, rifampin and pyrazinamide in the new pediatric HRZ FDC tablet.
Time frame: After at least 4 weeks of anti-TB therapy
Mean and median AUC0-8h of rifampin, isoniazid and pyrazinamide in children with TB treated with the new HRZ FDC tablet.
Cmax of isoniazid, rifampin and pyrazinamide in children with TB with and without HIV coinfection
Time frame: After at least 4 weeks of anti-TB therapy
Geometric mean values of Cmax of rifampin, isoniazid and pyrazinamide in children with HIV/TB coinfection compared to those with TB alone.
AUC0-8h of isoniazid, rifampin and pyrazinamide in children with TB with and without HIV coinfection.
Time frame: After at least 4 weeks of anti-TB therapy
Geometric mean values of AUC0-8h of rifampin, isoniazid and pyrazinamide in children with HIV/TB coinfection compared to those with TB alone.
4 secondary outcomes
AUC0-8h of isoniazid, rifampin and pyrazinamide in the new versus old pediatric HRZ FDC tablet.
Time frame: After at least 4 weeks of anti-TB therapy
Cmax of isoniazid, rifampin and pyrazinamide in the new versus old pediatric HRZ FDC tablet.
Time frame: After at least 4 weeks of anti-TB therapy
Proportion of children treated with new pediatric HRZ FDC tablet who develop with liver enzymes elevations.
Time frame: After at least 4 weeks of anti-TB therapy
Identify optimal weight-band dosages of the new HRZ FDC tablet
Time frame: After at least 4 weeks of anti-TB therapy
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 25 Nov 2024.
- Individual participant dataSharing planned: Undecided
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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.
Awewura Kwara, MD principal investigator
University of Florida
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 and Human Immunodeficiency Virus, run by University of Florida at 1 site in Ghana.
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 2 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 25 Nov 2024. 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 Ghana. 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?
Peak concentration (Cmax) of isoniazid, rifampin and pyrazinamide in the new pediatric HRZ FDC tablet. (time frame: After at least 4 weeks of anti-TB therapy). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2024.