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The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance (VITA 2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01187719
First received: August 23, 2010
Last updated: September 17, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
HIV-infection
Pregnancy
Mother to Child Transmission
 Drug: phenytoin
 Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 66
Study Start Date: May 2010
Study Completion Date: September 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 Drug: phenytoin
phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01187719

Locations
Tanzania
Kilimanjaro Christian Medical Centre
Moshi, Kilimanjaro region, Tanzania
Zambia
University Teaching Hospital
Lusaka, Zambia
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Elton Kisanga, PharmD, PhD Kilimanjaro Christian Medical Centre
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01187719     History of Changes
Other Study ID Numbers: UMCN-AKF 09.02
Study First Received: August 23, 2010
Last Updated: September 17, 2012
Health Authority: Tanzania: National Institute for Medical Research

Keywords provided by Radboud University:
HIV
pregnancy
phenytoin
ARV prophylaxis
nevirapine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Phenytoin
Nevirapine
 Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 17, 2012