Official Title: “The Effect of Single Dose Carbamazepine on the Pharmacokinetics of Single Dose Nevirapine (Viramune, NVP) and Development of NVP Resistance, PMTCT Program of Moshi, Tanzania (VITA1)”

Primary - pharmacokinetics of single dose nevirapine - the effect of single dose carbamazepine on the pk of single dose nevirapine - resistance against nevirapine before and after. - follow-up on HIV status newborns - relation between nevirapine levels in cord blood and plasma

Secondary - safety of single dose nevirapine and nevirapine/carbamazepine

Hypothesis:

Single dose carbamazepine decreases development of resistance to nevirapine in HIV positive pregnant Tanzanian women by decreasing nevirapine half-life.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study

Study Primary Completion Date: December 2008

Without the use of preventative measures, the risk of mother-to-child transmission (MTCT) of HIV-1 is estimated to vary between 25 and 48%. The regimen of single dose of nevirapine to the mother just before delivery and a single dose of nevirapine to the newborn within 24 - 72 hours after birth reduces the risk of MTCT by 50%, is affordable in many situations and is therefore standard of care in many African countries, like Tanzania. Recent studies, however, have shown that this single dose to the mother can induce the occurrence of nevirapine resistance in a large number of mothers. The mechanism of occurrence of nevirapine resistance already after a single dose is most likely related to the long elimination half-life of the drug. The subtherapeutic plasma levels present the perfect environment for the occurrence of resistance as the concentrations are subinhibitory for several days.

Intervention(s) in this Clinical Trial

• Drug: carbamazepine and nevirapine
  • Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.
• Drug: Nevirapine
  • Nevirapine 200mg is taken prior to delivery during labor.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Carbamazepine
  • An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery
• Placebo Comparator: Nevirapine
  • Standard therapy of 200mg Nevirapine oral prior to delivery

Primary Measures

• Cord blood will be taken less than 30 minutes after delivery
  • Time Frame: 0 - 30 min after delivery
    
• Blood samples from mother will be taken less than 30 minutes after delivery to measure viral load and CD4 count.
  • Time Frame: 0 - 30 min after delivery
    
• Blood samples will be drawn from mother and child at week 1 (day 6-8), week 2 (day 13-15) and week 3 (day 20-22)
  • Time Frame: day 6 - 22 after delivery
    
• From all samples plasma nevirapine and if applicable carbamazepine levels will be determined in women and newborns.
  • Time Frame: 0 30 min after delivery - week 3 after delivery
    

Inclusion Criteria:

• HIV infected
• antiretroviral naive
• not intending to relocate out of area during study
• willing to adhere to follow up scheme
• ability and willing to give written consent
• pregnant between 18 and 40 years
• willing and able to regularly attend the Antenatal clinic

Exclusion Criteria:

• serious illness that requires systemic treatment or hospitalization
• any condition that would compromise subject's ability to participate
• previously treated for HIV with antiretroviral agents, including single dose nevirapine used for MTCT
• inability to understand the nature and extent of the trial and procedures

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Radboud University

Overall Clinical Trial Officials and Contacts

David M. Burger, Dr. Principal Investigator Radboud University (RUNMC)  

Overall Contact: Eva P. Muro, PhamD +255 748468553 muroeva123@yahoo.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00294892

Study ID Number: VITA1

ClinicalTrials.gov Identifier: NCT00294892

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)