Health Trials

Dolutegravir Pharmacokinetics Among HIV/TB Coinfected Children Receiving Standard and High-dose Rifampicin

ConditionsPediatric HIV InfectionTuberculosis Infection
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age4-5
SponsorBrigham and Women's Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • rifampicin

    Drug

    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

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: Dolutegravir PK during standard and high-dose rifampicinExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Dolutegravir AUC during standard-dose rifampicin

Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature

Time frame
week 20
2

Dolutegravir AUC during high-dose rifampicin

Dolutegravir AUC will be compared against therapeutic ranges established in the literature and during standard-dose rifampicin

Time frame
week 22

Secondary outcomes

1

Rifampicin maximum concentration (Cmax) during standard-dose rifampicin

Rifampicin Cmax will be determined during standard rifampicin

Time frame
week 20
2

Rifampicin Cmax during high-dose rifampicin

Rifampicin Cmax will be determined during high-dose rifampicin and compared to that observed during standard-dose rifampicin

Time frame
week 22
3

Proportion of participants experiencing severe (grade 3 or 4) clinical or laboratory adverse events

Laboratory and clinical toxicities are monitored at 8 time points throughout the study and the proportion of children experiencing severe adverse events will be determined

Time frame
Week 48

Other outcomes

Sponsors and contacts

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Brigham and Women's Hospital

Lead sponsor

APIN Public Health Initiatives

Collaborator

University of Cape Town

Collaborator

Source ClinicalTrials.gov
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