The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance
Information source: Radboud University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV-infection; Pregnancy; Mother to Child Transmission
Intervention: phenytoin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Radboud University Official(s) and/or principal investigator(s): Elton Kisanga, PharmD, PhD, Principal Investigator, Affiliation: Kilimanjaro Christian Medical Centre
Summary
The primary objective of this two-phase trial is as follows:
- To determine the elimination half-life of NVP in HIV positive pregnant women
receiving it as a single dose in labour in addition to the ZDV and 3TC with or without
seven days phenytoin (pilot PK phase)
- To determine NVP resistance in HIV positive pregnant women receiving it as a single
dose in labour in addition to ZDV and 3TC with or without seven days phenytoin (main
trial phase)
The secondary objectives of this two-phase trial are as follows:
- To determine the safety of single dose nevirapine with seven days phenytoin as a part
of ARV prophylaxis for PMTCT vs. single dose of nevirapine without phenytoin as a part
of ARV prophylaxis for PMTCT
- To determine the HIV status of the infant
- To determine the safety of the ARV prophylaxis for PMTCT with seven days of phenytoin
on the newborn
Hypothesis: phenytoin reduces the elimination half life of SD NVP and thereby decreases
development of resistance to NVP in HIV positive pregnant Tanzanian and Zambian women.
Clinical Details
Official title: The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance After a Single Dose Nevirapine (VIramune®), Which is Part of ARV Prophylaxis for PMTCT in Moshi, TAnzania, and in Lusaka, Zambia (VITA2 Trial)
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: half-life time nevirapine
Secondary outcome: NVP resistancesafety of co-administration phenytoin and NVP HIV status of the newborn
Detailed description:
This trial (VITA2) will be done with phenytoin as enzyme inducer to decrease the elimination
half-life of NVP as it has also shown a significant difference in the elimination half-life
of NVP in the ENVI study and side effects were also transient and mild. The guidelines for
ARV prophylaxis for PMTCT has been changed to a more complex regimen. Therefore addition of
phenytoin OD for 7 days after delivery will not complicate the regimen for the mother.
Tanzania and Zambia are among the countries in sub-Saharan Africa most affected by the HIV
pandemic. In 2008, an estimated 85,000 children were living with HIV in Zambia and out of
the 89,000 children born to HIV infected women, 28,000 are infected annually. In Tanzania,
140,000 children were living with HIV in 2007. Both countries use NVP alone or in
combination with other drugs as ARV prophylaxis for PMTCT. Little data are available on the
extent of NVP resistance in the Tanzanian, Zambian PMTCT setting. Moreover, there is no data
available on the follow-up of mother-infant pair with particular focus on resistance to NVP
and the infants HIV status. No studies have explored possibilities of reducing NVP
resistance by use of an enzyme inducer.
This study seeks to the effect of phenytoin on the pharmacokinetics of NVP and the
development of NVP resistance on SD NVP as part of the ARV prophylaxis for PMTCT. This
intervention will be part of the VITA2 trial to test the hypothesis that phenytoin reduces
the elimination half life of SD NVP and thereby decreases development of resistance to NVP
in HIV positive pregnant Tanzanian and Zambian women.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- HIV-infected as documented by positive HIV antibody test
- Antiretroviral naïve
- Starting ARV prophylaxis from 28th weeks of gestation or at least 4 weeks before
delivery
- Not intending to relocate out of the area for the duration of study participation
- Willingness of subject to adhere to follow up schedule (note: this is more intensive
for the pilot PK phase)
- Ability and willingness of subject to give written consent
- Pregnant women aged 18 years and above
- Willing and able to regularly attend the antenatal clinic
Exclusion Criteria:
- Serious illness that requires systemic treatment or hospitalization
- Use of concomitant medication, which interferes with the ARV prophylaxis for PMTCT or
phenytoin
- Any condition that in the opinion of the investigator would compromise the subjects'
ability to participate in the study
- Previously treated for HIV infection with antiretroviral agents, including ARV
prophylaxis for PMTCT
- Inability to understand the nature and extent of the trial and the procedures
required
- CD4 count <350 cells/µl because such a patient is eligible for HAART
Locations and Contacts
University Teaching Hospital, Lusaka, Zambia
Kilimanjaro Christian Medical Centre, Moshi, Kilimanjaro region, Tanzania
Additional Information
Starting date: May 2010
Last updated: September 17, 2012
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