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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine (ZDV)
Drug: Didanosine (ddI)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • 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 ]

Enrollment: 244
Study Start Date: December 2004
Study Completion Date: February 2009
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    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
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00142337

Locations
Thailand
Chacheongsao Hospital
Muang, Chacheongsao, Thailand, 24000
Prapokklao Hospital
Muang, Chantaburi, Thailand, 22000
Nakornping Hospital
Mae Rim, Chiang Mai, Thailand, 50180
Health Promotion Center Region 10
Muang, Chiang Mai, Thailand, 50100
Lamphun Hospital
Munag, Chiang Mai, Thailand, 51000
Mae Chan Hospital
Mae Chan, Chiang Rai, Thailand, 57110
Mae Sai Hospital
Mae Sai, Chiang Rai, Thailand, 57130
Phan Hospital
Phan, Chiang Rai, Thailand, 57120
Chiangrai Prachanukroh Hospital
Muang, Chiangrai, Thailand, 57000
Chonburi Hospital
Muang, Chonburi, Thailand, 20000
Kalasin Hospital
Muang, Kalasin, Thailand, 46000
Phaholpolphayuhasena Hospital
Munag, Kanjanaburi, Thailand, 71000
Kranuan Crown Prince Hospital
Kranuan, Khon Kaen, Thailand, 40170
Khon Kaen Hospital
Muang, Khon Kaen, Thailand, 40000
Srinagarind Hospital
Muang, Khon Kaen, Thailand, 40002
Regional Health Promotion Centre 6, Khon Kaen
Muang, Khon Kaen, Thailand, 40000
Lampang Hospital
Muang, Lampang, Thailand, 52000
Nakhonpathom Hospital
Muang, Nakhonpathom, Thailand, 73000
Maharaj Nakornratchasrima Hospital
Muang, Nakornratchasrima, Thailand, 30000
Nong Khai Hospital
Muang, Nong Kai, Thailand, 43000
Pranangklao Hospital
Muang, Nonthaburi, Thailand, 11000
Chiang Kham Hospital
Chiang Kham, Phayao, Thailand, 56110
Buddhachinaraj Hospital
Muang, Pitsanuloke, Thailand, 65000
Ratchaburi Hospital
Muang, Ratchaburi, Thailand, 70000
Rayong Hospital
Muang, Rayong, Thailand, 21000
Roi-et Hospital
Muang, Roi-et, Thailand, 45000
Samutsakorn Hospital
Muang, Samutsakorn, Thailand, 74000
Hat Yai Hospital
Hat Yai, Songkla, Thailand, 90110
Health Promotion Hospital Regional Center I
Bangkok, Thailand, 10220
Bhumibol Adulyadej Hospital
Bangkok, Thailand, 10220
Somdej Pranangchao Sirikit Hospital
Chonburi, Thailand, 20180
Samutprakarn Hospital
Samutprakarn, Thailand, 10280
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Investigators
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement
  More Information

Publications:

Responsible Party: Marc Lallemant, Senior Researcher, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00142337     History of Changes
Other Study ID Numbers: IRD-UMI 174 PHPT-4
Study First Received: September 1, 2005
Last Updated: January 4, 2012
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
zidovudine
didanosine
Prevention of mother to child transmission of HIV
nevirapine
Thailand
Resistance
HIV
Postpartum period

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Didanosine
Nevirapine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014