Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04437836 |
| Other study ID # |
TMA2017CDF-1876-HighRif C |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2019 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
December 2023 |
| Source |
Kilimanjaro Clinical Research Institute |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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 (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.
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.
