Health Trials

Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

ConditionsPediatric HIV InfectionLatent Tuberculosis
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age4-11
SponsorBrigham and Women's Hospital

About this trial

Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Short-course TB prevention/latent TB infection (LTBI) treatment regimens increase completion rates but have not been adequately studied among children living with HIV. Our prospective, open-label PK study will examine and extend use of weekly rifapentine and isoniazid (3HP) among children receiving dolutegravir. This will address gaps in knowledge by examining two-way PK of short-course LTBI treatment in a vulnerable pediatric population.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

(1) ART-naïve or ART-experienced HIV-infected children 4 weeks to <12 years of age;

(2) no evidence of active TB based on an appropriate clinical evaluation;

(3) negative TB diagnostic test if performed (other than tuberculin skin testing);

(4) weight of at least 4 kilograms; and

Disqualifiers

(1) Baseline labs with evidence of ≥grade 3 abnormalities: alanine aminotransferase (ALT), total bilirubin, absolute neutrophil count (ANC), platelets, creatinine;

(2) presenting with acute respiratory distress or decompensation, or any clinical syndrome which could suggest undiagnosed TB or other opportunistic infection; or

(3) receipt of a medication that has drug-drug interactions with DTG or RPT.

Trial design

Design model

Single group

Treatments tested in this trial

  • Rifapentine

    Drug

    Children 2-11 years received standard HIV treatment and 3HP (RPT/INH weekly for 12 weeks) for TB prevention. Children \<2 years receive standard HIV treatment, a single-dose of extrapolated weekly RPT/INH, followed by standard INH prophylaxis. Safety and pharmacokinetics will be evaluated.

  • Dolutegravir

    Drug

    All children in this study are living with HIV and thus dolutegravir is a standard part of treatment; in this study we will collect blood samples to measure dolutegravir levels during combination treatment with rifapentine/isoniazid treatment for TB prevention

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Dolutegravir PK during weekly rifapentine/isoniazid for TB preventionExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dolutegravir AUC during weekly rifapentine/isoniazid

Dolutegravir area under the concentration time curve (AUC) will be compared to therapeutic ranges established in the adult and pediatric literature. Intensive PK sampling will occur at week 6 for dolutegravir and rifapentine PK. Week 4 sparse PK sampling will provide dolutegravir exposures without rifapentine.

Time frame
Weeks 4 and 6

Secondary outcomes

1

Rifapentine AUC

Rifapentine AUC will be compared against adult targets. Week 7 sparse PK will provide weekly Cmin estimate.

Time frame
weeks 6 and 7
2

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

Laboratory and clinical toxicities are monitored at 8-9 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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