The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance

NCT01187719 | Completed Phase 2 DMC

• 1 other identifier: UMCN-AKF 09.02
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

HIV-infection; Pregnancy; Mother to Child Transmission

Keywords

HIV; pregnancy; phenytoin; ARV prophylaxis; nevirapine

Outcome Measures

Primary Outcomes (1)

• 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

  untill two weeks after NVP dosing

Secondary Outcomes (3)

• NVP resistance

  week 4 / week 6 after delivery

• safety of co-administration phenytoin and NVP

  entire trial

• HIV status of the newborn

  week 6 after birth

Study Arms (2)

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

Drug: phenytoin

Interventions

phenytoin DRUG

phenytoin 184 mg (2 tablets of 92mg) OD at onset of labour and continue for seven days

phenytoin interaction

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (2)

Kilimanjaro Christian Medical Centre

Moshi, Kilimanjaro, Tanzania

Location

University Teaching Hospital

Lusaka, Zambia

Location

Related Publications (1)

• 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.

  PMID: 23864647 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Phenytoin

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Elton Kisanga, PharmD, PhD

  Kilimanjaro Christian Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2010
• First Posted: August 24, 2010
• Study Start: May 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 1, 2020

Record last verified: 2020-11

Locations

TA (1); ZA (1)