The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance (VITA 2)
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.
Mother to Child Transmission
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|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)|
- half-life time nevirapine [ Time Frame: untill two weeks after NVP dosing ] [ Designated as safety issue: No ]blood samples will be taken <30 min after delivery, 24 hours after delivery, at day 3, at day 5, at day 7 and at day 14
- NVP resistance [ Time Frame: week 4 / week 6 after delivery ] [ Designated as safety issue: No ]resistance testing at week 4 or week 6 after delivery (and NVP dosing).
- safety of co-administration phenytoin and NVP [ Time Frame: entire trial ] [ Designated as safety issue: Yes ]Adverse events will be collected during the entire trial (for both mother and child).
- HIV status of the newborn [ Time Frame: week 6 after birth ] [ Designated as safety issue: Yes ]HIV status of the newborn will be assessed at week 6 after birth.
|Study Start Date:||May 2010|
|Study Completion Date:||September 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
No Intervention: Control
ARV prophylaxis for PMTCT follows national guidelines.
Experimental: phenytoin interaction
ARV prophylaxis for PMTCT follows national guidelines + start phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days
phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01187719
|Kilimanjaro Christian Medical Centre|
|Moshi, Kilimanjaro region, Tanzania|
|University Teaching Hospital|
|Principal Investigator:||Elton Kisanga, PharmD, PhD||Kilimanjaro Christian Medical Centre|