Clinical TrialPhase 1/2HighRif CNCT04437836
Evaluation of Pharmacokinetics and Safety Tolerability of Higher Doses of Rifampic
A Phase 1/2 study testing Evaluation of high dose rifampicin in children in people with Clinical Trial, run by Kilimanjaro Clinical Research Institute at 4 sites in Tanzania.
Trial summary
Tuberculosis in children is a major public health problem and it contributes 10% of the total TB cases worldwide. TB treatment outcomes in children are challenged by insufficient consideration of the relationships between doses administered, concentrations achieved and eventual desirable and undesirable effects… Read more about this study
- Who is it for?
- Ages 1 year to 14 years
- Conditions the study is for
- Clinical Trial
- What is being tested?
- Evaluation of high dose rifampicin in children
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 4 sitesTanzania
- Study dates
- 1 Jul 2019to 31 Dec 2023
- Phase
- Phase 1/2
- 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 1 year to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged 1 to 14 years with newly diagnosed Tuberculosis
Who cannot join
- Children with elevated liver function
- Children allergic to first line anti-TB drugs
Trial locations and contacts
4 sites in 1 country.
Tanzania4 sites
Mt. Meru Hospital
Arusha
Hydom Hospital
Babati, Manyara Region
Kilimanjaro Clinical Research Institute
Moshi, Kilimanjaro, +255
Huruma Hospital
Moshi
About this study
Official title: Evaluation of Pharmacokinetics and Safety Tolerability of Higher Doses of Rifampicin in Children With Newly Diagnosed Uncomplicated Tuberculosis
Tuberculosis in children is a major public health problem and it contributes 10% of the total TB cases worldwide. TB treatment outcomes in children are challenged by insufficient consideration of the relationships between doses administered, concentrations achieved and eventual desirable and undesirable effects (pharmacodynamics) of TB drugs. Rifampicin is a pivotal TB drug and data from adults suggest that a much higher dose of rifampicin (35 mg/kg instead of 10 mg/kg), resulting in much higher rifampicin exposures in plasma, is safe and tolerable and may provide a higher efficacy. The dose needed in children to achieve the same exposure in plasma is unknown.
Read the detailed description
Tuberculosis (TB) in children is a major public health problem . It has a global estimate of >100,000 deaths per year and is included in the top ten causes of mortality in children worldwide. Children contribute 10% of the total TB cases worldwide. More than 75% of the worldwide estimated cases of TB in children occur in the 30 high burden countries, Tanzania being one of them. The enormous burden of pediatric TB in these countries is due to the TB epidemic amongst adults and the simultaneous HIV pandemic and a child less than 14 years of age whether HIV infected or not is at a high risk of developing the disease. Subsequent dissemination of the mycobacterium and progression of the disease is also fast in children.
Knowledge on the efficacy and safety of medicines for children is still very limited and sometimes children are still being treated as small adults. However, adult dosing cannot be logically extrapolated to children according to weight or age because of different pharmacokinetics, i.e. the relationship between doses administered and exposures (drug concentrations) achieved, in children as compared with adults . More specifically, these pharmacokinetic differences occur in the subsequent processes of absorption, distribution, metabolism and elimination of drugs, which are subject to physiological changes due to growth and development in children. Especially in young children, maturation of liver metabolism pathways and renal function are not completed.
In contrast, the pharmacodynamics of a drug, i.e. the relationship between concentrations achieved and eventual response is generally considered similar between adults and children, although differences in drug metabolism between children and adults may lead to differences in susceptibility to some adverse drug reactions. Thus, because of the differences in pharmacokinetics in children with different ages, they should not receive the same drug doses on mg/kg base as adults, and drug dosage selection in children should rather be based upon stages of growth and development. These drug doses should target the exposures that are efficacious in adults.
- Conditions
- Clinical Trial
- Being tested
- Evaluation of high dose rifampicin in children
- Keywords
- Tuberculosis, Pharmacokinetics, safety/torelability
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evaluation of high dose rifampicin in childrenDrug
Also called Safety monitoring
Evaluation of severity of adverse event from grade 1 to 5
| Study group | Role | What they receive |
|---|---|---|
| Control arm | Experimental | Participants will receive standard treatment of rifampicin Receives: Drug: Evaluation of high dose rifampicin in children |
| First High dose | Experimental | Participants will receive 30mg per kg body weight of rifampicin Receives: Drug: Evaluation of high dose rifampicin in children |
| Second high dose | Experimental | Particpants will receive 40mg per kg body weight of rifampicin Receives: Drug: Evaluation of high dose rifampicin in children |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of high dose rifampicin
To know the maximum tolerable dose of rifampicin in children aged 1-14 years
Measured: 54 months
Secondary outcomes (2)
Plasma concentration
Maximum observed concentration
Measured: 54 months
Time
To measure time to reach maximum concentration
Measured: 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2020
- Study start1 Jul 2019
- Primary completion30 Jun 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical TrialStudies 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Safety and tolerability study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kilimanjaro Clinical Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04437836
- Sponsor's protocol ID
- TMA2017CDF-1876-HighRif C
- Acronym
- HighRif C
- Status last verified
- Dec 2023
- First submitted
- 28 May 2020
- Last updated
- 15 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Pharmacokinetics and Safety Tolerability of Higher Doses of Rifampicin in Children With Newly Diagnosed Uncomplicated Tuberculosis
- ClinicalTrials.gov ID
- NCT04437836
- Acronym / sponsor ID
- HighRif C / TMA2017CDF-1876-HighRif C
- Conditions
- Clinical Trial
- Keywords
- Tuberculosis, Pharmacokinetics, safety/torelability
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Kilimanjaro Clinical Research InstituteUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Jun 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Jun 2020 (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.
Tuberculosis in children is a major public health problem and it contributes 10% of the total TB cases worldwide. TB treatment outcomes in children are challenged by insufficient consideration of the relationships between doses administered, concentrations achieved and eventual desirable and undesirable effects (pharmacodynamics) of TB drugs. Rifampicin is a pivotal TB drug and data from adults suggest that a much higher dose of rifampicin (35 mg/kg instead of 10 mg/kg), resulting in much higher rifampicin exposures in plasma, is safe and tolerable and may provide a higher efficacy. The dose needed in children to achieve the same exposure in plasma is unknown.
Detailed description
Tuberculosis (TB) in children is a major public health problem . It has a global estimate of >100,000 deaths per year and is included in the top ten causes of mortality in children worldwide. Children contribute 10% of the total TB cases worldwide. More than 75% of the worldwide estimated cases of TB in children occur in the 30 high burden countries, Tanzania being one of them. The enormous burden of pediatric TB in these countries is due to the TB epidemic amongst adults and the simultaneous HIV pandemic and a child less than 14 years of age whether HIV infected or not is at a high risk of developing the disease. Subsequent dissemination of the mycobacterium and progression of the disease is also fast in children.
Knowledge on the efficacy and safety of medicines for children is still very limited and sometimes children are still being treated as small adults. However, adult dosing cannot be logically extrapolated to children according to weight or age because of different pharmacokinetics, i.e. the relationship between doses administered and exposures (drug concentrations) achieved, in children as compared with adults . More specifically, these pharmacokinetic differences occur in the subsequent processes of absorption, distribution, metabolism and elimination of drugs, which are subject to physiological changes due to growth and development in children. Especially in young children, maturation of liver metabolism pathways and renal function are not completed.
In contrast, the pharmacodynamics of a drug, i.e. the relationship between concentrations achieved and eventual response is generally considered similar between adults and children, although differences in drug metabolism between children and adults may lead to differences in susceptibility to some adverse drug reactions. Thus, because of the differences in pharmacokinetics in children with different ages, they should not receive the same drug doses on mg/kg base as adults, and drug dosage selection in children should rather be based upon stages of growth and development. These drug doses should target the exposures that are efficacious in adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Safety and tolerability study
| Arm | Type | Receives |
|---|---|---|
| Control arm | Experimental | Drug: Evaluation of high dose rifampicin in childrenParticipants will receive standard treatment of rifampicin |
| First High dose | Experimental | Drug: Evaluation of high dose rifampicin in childrenParticipants will receive 30mg per kg body weight of rifampicin |
| Second high dose | Experimental | Drug: Evaluation of high dose rifampicin in childrenParticpants will receive 40mg per kg body weight of rifampicin |
Who may qualify
- Ages
- 1 year to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Children aged 1 to 14 years with newly diagnosed Tuberculosis
Key exclusion criteria (2 listed)
- Children with elevated liver function
- Children allergic to first line anti-TB drugs
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 |
|---|---|---|
| Evaluation of high dose rifampicin in childrenAlso: Safety monitoringEvaluation of severity of adverse event from grade 1 to 5 | Drug | Control arm, First High dose, Second high dose |
Primary outcome
Evaluation of high dose rifampicin
Time frame: 54 months
To know the maximum tolerable dose of rifampicin in children aged 1-14 years
2 secondary outcomes
Plasma concentration
Time frame: 54 months
Time
Time frame: 54 months
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 15 Feb 2024.
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Evaluation of high dose rifampicin in children in people with Clinical Trial, run by Kilimanjaro Clinical Research Institute at 4 sites in Tanzania.
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 1 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 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Tanzania. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Evaluation of high dose rifampicin (time frame: 54 months). 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 15 Feb 2024.