Pharmacokinetics Study on Nevirapine Resistance in Tanzania

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT00294892
First received: February 21, 2006
Last updated: May 30, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: carbamazepine and nevirapine
Drug: Nevirapine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Cord blood will be taken less than 30 minutes after delivery [ Time Frame: 0 - 30 min after delivery ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 144
Study Start Date: February 2006
Study Completion Date: June 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Carbamazepine
An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery
Drug: carbamazepine and nevirapine
Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.
Placebo Comparator: Nevirapine
Standard therapy of 200mg Nevirapine oral prior to delivery
Drug: Nevirapine
Nevirapine 200mg is taken prior to delivery during labor.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00294892

Locations
Tanzania
Kilimanjaro Christian Medical College
Moshi, Tanzania
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: David M. Burger, Dr. Radboud University (RUNMC)
  More Information

Additional Information:
No publications provided by Radboud University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT00294892     History of Changes
Other Study ID Numbers: VITA1
Study First Received: February 21, 2006
Last Updated: May 30, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
HIV
mother to child transmission; MTCT
nevirapine resistance
pharmacokinetics
Treatment Naive

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
Carbamazepine
Nevirapine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 16, 2014