HIV-infectionPhase 2VITA 2NCT01187719
The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance
A Phase 2 study testing phenytoin in people with HIV-infection and Pregnancy, run by Radboud University Medical Center at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV-infection, Pregnancy, Mother to Child Transmission
- What is being tested?
- phenytoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 2 sitesin 2 countries
- Study dates
- May 2010to Sep 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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)
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)
Read more
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.
Read the 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.
- Conditions
- HIV-infection, Pregnancy, Mother to Child Transmission
- Being tested
- phenytoin
- Keywords
- HIV, pregnancy, phenytoin, ARV prophylaxis, nevirapine
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenytoinDrug
phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | ARV prophylaxis for PMTCT follows national guidelines. |
| phenytoin interaction | Experimental | 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 Receives: Drug: phenytoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
half-life time nevirapine
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
Measured: untill two weeks after NVP dosing
Secondary outcomes (3)
NVP resistance
resistance testing at week 4 or week 6 after delivery (and NVP dosing).
Measured: week 4 / week 6 after delivery
safety of co-administration phenytoin and NVP
Adverse events will be collected during the entire trial (for both mother and child).
Measured: entire trial
HIV status of the newborn
HIV status of the newborn will be assessed at week 6 after birth.
Measured: week 6 after birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2010 (estimated)
- Study startMay 2010
- Primary completionJun 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-infectionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elton Kisanga, PharmD, PhD, Principal investigator, Kilimanjaro Christian Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01187719
- Sponsor's protocol ID
- UMCN-AKF 09.02
- Acronym
- VITA 2
- Status last verified
- Nov 2020
- First submitted
- 23 Aug 2010
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fillekes Q, Muro EP, Chunda C, Aitken S, Kisanga ER, Kankasa C, Thomason MJ, Gibb DM, Walker AS, Burger DM. Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. J Antimicrob Chemother. 2013 Nov;68(11):2609-15. doi: 10.1093/jac/dkt246. Epub 2013 Jul 17.
PubMed 23864647
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01187719
- Acronym / sponsor ID
- VITA 2 / UMCN-AKF 09.02
- Conditions
- HIV-infection, Pregnancy, Mother to Child Transmission
- Keywords
- HIV, pregnancy, phenytoin, ARV prophylaxis, nevirapine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 24 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –ARV prophylaxis for PMTCT follows national guidelines. |
| phenytoin interaction | Experimental | Drug: phenytoinARV prophylaxis for PMTCT follows national guidelines + start phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| phenytoinphenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days | Drug | phenytoin interaction |
Primary outcome
half-life time nevirapine
Time frame: untill two weeks after NVP dosing
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
3 secondary outcomes
NVP resistance
Time frame: week 4 / week 6 after delivery
safety of co-administration phenytoin and NVP
Time frame: entire trial
HIV status of the newborn
Time frame: week 6 after birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Results publication: PubMed 23864647Fillekes Q, Muro EP, Chunda C, Aitken S, Kisanga ER, Kankasa C, Thomason MJ, Gibb DM, Walker AS, Burger DM. Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial. J Antimicrob Chemother. 2013 Nov;68(11):2609-15. doi: 10.1093/jac/dkt246. Epub 2013 Jul 17.
Related trials for HIV-infection
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elton Kisanga, PharmD, PhD principal investigator
Kilimanjaro Christian Medical Centre
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing phenytoin in people with HIV-infection and Pregnancy, run by Radboud University Medical Center at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Tanzania, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
half-life time nevirapine (time frame: untill two weeks after NVP dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01187719, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2020.