Dolutegravir Pharmacokinetics Among HIV/TB Coinfected Children Receiving Standard and High-dose Rifampicin
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: rifampicin.
- Кому может быть актуально
- Состояния в реестре: Pediatric HIV Infection, Tuberculosis Infection. Базовые параметры: 4 Weeks — 5 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Nigeria
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Официальное название
Mind the Gaps: Pharmacokinetic Research to Advance Pediatric HIV/TB Cotreatment and TB Prevention
Обзор
Tuberculosis (TB) is the leading cause of death among children with HIV, yet insufficient data are available on the pharmacokinetics of newer HIV/TB cotreatment strategies in children. Current WHO-recommended rifampicin dosages result in low concentrations in most children, and high-dose rifampicin may improve outcomes and shorten treatment duration. Yet the impact of high-dose rifampicin on dolutegravir exposures has not been examined in children. This study aims to evaluate the safety and pharmacokinetics of dolutegravir twice daily among HIV/TB coinfected children receiving standard-dose and high-dose rifampicin.
Подробное описание
This study is a prospective, single-arm, open-label, intensive and sparse pharmacokinetic (PK) and safety study to evaluate steady-state dolutegravir (DTG) concentrations among 20 HIV/TB coinfected children 4 weeks to \<6 years of age requiring concurrent TB treatment. Ten patients will be recruited into each of two age cohorts: 4 weeks to \<2 years and ≥2 years to \<6 years.
Children will be recruited from two large pediatric HIV clinics in Nigeria. Children in this study will receive HIV/TB cotreatment that is considered standard of care consisting of DTG twice daily during rifampicin (RIF)-containing TB treatment. For this portion of the study, the primary intervention is additional blood sampling for drug concentration determination and biomarker assessment. Additionally, during a two week period (study weeks 20-21), the RIF dose will be increased from standard-dose to high-dose RIF, during which two-way PK and toxicity monitoring will occur. Clinical and laboratory monitoring for toxicity during HIV/TB cotreatment is consistent with routine care.
PK sampling for drug concentration determination will occur at three time points during the 48-week study. Specifically, PK sampling will occur at week-20 to evaluate DTG twice daily during standard-dose RIF, week-22 to evaluate DTG twice daily during high-dose RIF, and at week-30 to evaluate DTG once daily after TB treatment is complete.
Additionally, the endogenous biomarker of CYP3A4 activity, 4-beta-hydroxycholesterol to cholesterol ratio, will be evaluated to advance understanding of underlying mechanisms of drug action. Blood sampling to quantify this biomarker will occur at either 4 (among ART-experienced children) or 5 (ART-naive) time points during the 48-week study.
Вмешательства
- Препарат rifampicin
Patients will receive standard TB and HIV treatment, however, for two weeks (study weeks 20-21) the dose of rifampicin will be increased from standard-dose to high-dose to assess pharmacokinetics and safety
Первичные конечные точки
- Dolutegravir AUC during standard-dose rifampicin [Срок оценки: week 20]
- Dolutegravir AUC during high-dose rifampicin [Срок оценки: week 22]
Вторичные конечные точки (3)
- Rifampicin maximum concentration (Cmax) during standard-dose rifampicin [Срок оценки: week 20]
- Rifampicin Cmax during high-dose rifampicin [Срок оценки: week 22]
- Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events [Срок оценки: Week 48]
Критерии участия
Критерии включения
- ART-naïve or ART-experienced HIV-infected children between 4 weeks and <6 years of age
- Active TB diagnosis
- Weight of at least 3 kilograms
- Consent of the parent or legal guardian
Критерии исключения
- Baseline labs with evidence of ≥grade 3 abnormalities: ALT, total bilirubin, absolute neutrophil count (ANC), platelets, or creatinine
- Suspected TB meningitis or presenting with acute respiratory distress or decompensation
- Receipt of a medication that has drug-drug interactions with dolutegravir or rifampicin
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Распределение
- Не применимо
- Модель
- Одна группа
- Маскирование
- Открытое
- Основная цель
- Лечение
Центры проведения
Nigeria · 1 центр
- University College Hospital/ University of Ibadan — Ibadan
Идентификаторы
NCT: NCT05069688 · 2021P002401