One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Marc Lallemant, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00142337
First received: September 1, 2005
Last updated: January 4, 2012
Last verified: January 2012

September 1, 2005
January 4, 2012
December 2004
May 2006   (final data collection date for primary outcome measure)
Proportion of patients with viral NNRTI mutations detectable during the 4 month follow-up compared with the incidence observed in the PHPT-2 clinical trial, who received the same antiretroviral prophylaxis but no post-partum regimen [ Time Frame: Within 4 months postpartum ] [ Designated as safety issue: No ]
Proportion of patients with viral NNRTIs mutations detectable during the 4 month follow-up compared with the incidence observed in the PHPT-2 clinical trial, who received the same antiretroviral prophylaxis but no post-partum regimen
Complete list of historical versions of study NCT00142337 on ClinicalTrials.gov Archive Site
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One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine
A Phase 2, One Arm, Open Label, Feasibility Study Assessing One Month Zidovudine/Didanosine Postpartum Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine to Prevent Mother to Child Transmission of HIV

The purpose of this study is to determine whether providing zidovudine (ZDV) and didanosine (ddI) during labor and for one month postpartum can reduce the selection of nevirapine (NVP) resistance mutations postpartum in women who received a single dose of nevirapine during labor and standard ZDV prophylaxis for the prevention of mother to child transmission of HIV.

A single nevirapine dose to the mother, with or without a dose to the child, in addition to oral ZDV prophylaxis starting from 28 weeks gestation has been proven to be highly effective in reducing further mother-to-child HIV transmission (PMTCT).

However, post exposure nevirapine resistance mutations are observed in the mother's viral population. These mutations detectable very early after exposure tend to disappear over time.

Nevertheless, they may be associated with decrease in efficacy of non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens subsequently given to the women for their own health.

Therefore, there is a need for research to prevent selection of resistance in the first place or to overcome the resistance in subsequent treatment of the infected mother or infant.

Nevirapine plasma levels above IC50 have been detected in women exposed to a single 200 mg dose of nevirapine in a significant number of women during the third week postpartum.

We hypothesize that giving ZDV+ddI to women exposed to nevirapine for one month as soon as possible after exposure may prevent the selection of nevirapine resistance mutations.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
HIV Infections
  • Drug: Zidovudine (ZDV)
    Zidovudine 300 mg, twice daily, for one month postpartum. Note: after July 03, 2005, all women received 200 mg, twice daily, for the same duration.
  • Drug: Didanosine (ddI)
    250 mg ddI-EC (400 mg if body weight >60 kg) once daily, starting at the onset of labor and for one month postpartum
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
244
February 2009
May 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Meet all pre-entry criteria;
  • Consent to participate and to be followed for the duration of the study;
  • Present the following laboratory values within 14 days prior to inclusion:

    • Hemoglobin > 8.0 mg/dl
    • Absolute neutrophil count > 1000 cells/mm3
    • Platelets > 100,000 cells/mm3
    • Serum creatinine < 1.5 mg/dl (women with a serum creatinine > 1.5 mg/dl must have a measured eight-hour urine creatinine clearance > 70 ml/min)
    • SGPT less than 10 times the upper limit of normal
    • Amylase less than 150/L IU (this upper limit may change slightly depending on the normal range at the hospital laboratory).

Exclusion Criteria:

  • Evidence of pre-existing fetal anomalies incompatible with life;
  • Known hypersensitivity to any benzodiazepine or to NVP;
  • Receipt of antiretroviral agent other than ZDV;
  • Receipt of non-allowed concomitant treatment or contraindication to ddI
  • Concurrent participation in another clinical trial;
  • Women with a CD4 count <200/µL or history of oral candidiasis if they are not receiving pneumocystis carinii pneumonia (PCP) prophylaxis
  • Any other contra-indicated drugs during ZDV+ddI treatment for the mother as well as the child (Contra-indicated drugs such as gancyclovir, isoniazid, linezolid, ethambutol, rifabutin, cidofovir are not allowed during the ZDV ddI treatment after delivery in order to prevent pharmacological interactions or overlapping toxicities.)
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00142337
IRD-UMI 174 PHPT-4
Not Provided
Marc Lallemant, Institut de Recherche pour le Developpement
Institut de Recherche pour le Developpement
Not Provided
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement
Institut de Recherche pour le Developpement
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP