Back to resultsOne Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 2
Locations
Thailand
Study Type
Interventional
Intervention
Zidovudine (ZDV)
Didanosine (ddI)
Sponsored by
About this trial
This is an interventional prevention trial for HIV Infections focused on measuring zidovudine, didanosine, Prevention of mother to child transmission of HIV, nevirapine, Thailand, Resistance, HIV, Postpartum period
Eligibility 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.)
Sites / Locations
- Chacheongsao Hospital
- Prapokklao Hospital
- Nakornping Hospital
- Health Promotion Center Region 10
- Lamphun Hospital
- Mae Chan Hospital
- Mae Sai Hospital
- Phan Hospital
- Chiangrai Prachanukroh Hospital
- Chonburi Hospital
- Kalasin Hospital
- Phaholpolphayuhasena Hospital
- Kranuan Crown Prince Hospital
- Khon Kaen Hospital
- Regional Health Promotion Centre 6, Khon Kaen
- Srinagarind Hospital
- Lampang Hospital
- Nakhonpathom Hospital
- Maharaj Nakornratchasrima Hospital
- Nong Khai Hospital
- Pranangklao Hospital
- Chiang Kham Hospital
- Buddhachinaraj Hospital
- Ratchaburi Hospital
- Rayong Hospital
- Roi-et Hospital
- Samutsakorn Hospital
- Hat Yai Hospital
- Bhumibol Adulyadej Hospital
- Health Promotion Hospital Regional Center I
- Somdej Pranangchao Sirikit Hospital
- Samutprakarn Hospital
Outcomes
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
Secondary Outcome Measures
Full Information
NCT ID
NCT00142337
First Posted
September 1, 2005
Last Updated
January 4, 2012
Sponsor
Institut de Recherche pour le Developpement
1. Study Identification
Unique Protocol Identification Number
NCT00142337
Brief Title
One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
February 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherche pour le Developpement
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
zidovudine, didanosine, Prevention of mother to child transmission of HIV, nevirapine, Thailand, Resistance, HIV, Postpartum period
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
244 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Zidovudine (ZDV)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Didanosine (ddI)
Intervention Description
250 mg ddI-EC (400 mg if body weight >60 kg) once daily, starting at the onset of labor and for one month postpartum
Primary Outcome Measure Information:
Title
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
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Lallemant, MD
Organizational Affiliation
Institut de Recherche pour le Developpement
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chacheongsao Hospital
City
Muang
State/Province
Chacheongsao
ZIP/Postal Code
24000
Country
Thailand
Facility Name
Prapokklao Hospital
City
Muang
State/Province
Chantaburi
ZIP/Postal Code
22000
Country
Thailand
Facility Name
Nakornping Hospital
City
Mae Rim
State/Province
Chiang Mai
ZIP/Postal Code
50180
Country
Thailand
Facility Name
Health Promotion Center Region 10
City
Muang
State/Province
Chiang Mai
ZIP/Postal Code
50100
Country
Thailand
Facility Name
Lamphun Hospital
City
Munag
State/Province
Chiang Mai
ZIP/Postal Code
51000
Country
Thailand
Facility Name
Mae Chan Hospital
City
Mae Chan
State/Province
Chiang Rai
ZIP/Postal Code
57110
Country
Thailand
Facility Name
Mae Sai Hospital
City
Mae Sai
State/Province
Chiang Rai
ZIP/Postal Code
57130
Country
Thailand
Facility Name
Phan Hospital
City
Phan
State/Province
Chiang Rai
ZIP/Postal Code
57120
Country
Thailand
Facility Name
Chiangrai Prachanukroh Hospital
City
Muang
State/Province
Chiangrai
ZIP/Postal Code
57000
Country
Thailand
Facility Name
Chonburi Hospital
City
Muang
State/Province
Chonburi
ZIP/Postal Code
20000
Country
Thailand
Facility Name
Kalasin Hospital
City
Muang
State/Province
Kalasin
ZIP/Postal Code
46000
Country
Thailand
Facility Name
Phaholpolphayuhasena Hospital
City
Munag
State/Province
Kanjanaburi
ZIP/Postal Code
71000
Country
Thailand
Facility Name
Kranuan Crown Prince Hospital
City
Kranuan
State/Province
Khon Kaen
ZIP/Postal Code
40170
Country
Thailand
Facility Name
Khon Kaen Hospital
City
Muang
State/Province
Khon Kaen
ZIP/Postal Code
40000
Country
Thailand
Facility Name
Regional Health Promotion Centre 6, Khon Kaen
City
Muang
State/Province
Khon Kaen
ZIP/Postal Code
40000
Country
Thailand
Facility Name
Srinagarind Hospital
City
Muang
State/Province
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Lampang Hospital
City
Muang
State/Province
Lampang
ZIP/Postal Code
52000
Country
Thailand
Facility Name
Nakhonpathom Hospital
City
Muang
State/Province
Nakhonpathom
ZIP/Postal Code
73000
Country
Thailand
Facility Name
Maharaj Nakornratchasrima Hospital
City
Muang
State/Province
Nakornratchasrima
ZIP/Postal Code
30000
Country
Thailand
Facility Name
Nong Khai Hospital
City
Muang
State/Province
Nong Kai
ZIP/Postal Code
43000
Country
Thailand
Facility Name
Pranangklao Hospital
City
Muang
State/Province
Nonthaburi
ZIP/Postal Code
11000
Country
Thailand
Facility Name
Chiang Kham Hospital
City
Chiang Kham
State/Province
Phayao
ZIP/Postal Code
56110
Country
Thailand
Facility Name
Buddhachinaraj Hospital
City
Muang
State/Province
Pitsanuloke
ZIP/Postal Code
65000
Country
Thailand
Facility Name
Ratchaburi Hospital
City
Muang
State/Province
Ratchaburi
ZIP/Postal Code
70000
Country
Thailand
Facility Name
Rayong Hospital
City
Muang
State/Province
Rayong
ZIP/Postal Code
21000
Country
Thailand
Facility Name
Roi-et Hospital
City
Muang
State/Province
Roi-et
ZIP/Postal Code
45000
Country
Thailand
Facility Name
Samutsakorn Hospital
City
Muang
State/Province
Samutsakorn
ZIP/Postal Code
74000
Country
Thailand
Facility Name
Hat Yai Hospital
City
Hat Yai
State/Province
Songkla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Bhumibol Adulyadej Hospital
City
Bangkok
ZIP/Postal Code
10220
Country
Thailand
Facility Name
Health Promotion Hospital Regional Center I
City
Bangkok
ZIP/Postal Code
10220
Country
Thailand
Facility Name
Somdej Pranangchao Sirikit Hospital
City
Chonburi
ZIP/Postal Code
20180
Country
Thailand
Facility Name
Samutprakarn Hospital
City
Samutprakarn
ZIP/Postal Code
10280
Country
Thailand
12. IPD Sharing Statement
Citations:
PubMed Identifier
15247338
Citation
Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
15247339
Citation
Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
15735445
Citation
Cressey TR, Jourdain G, Lallemant MJ, Kunkeaw S, Jackson JB, Musoke P, Capparelli E, Mirochnick M. Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1. J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):283-8.
Results Reference
background
PubMed Identifier
20158398
Citation
Lallemant M, Ngo-Giang-Huong N, Jourdain G, Traisaithit P, Cressey TR, Collins IJ, Jarupanich T, Sukhumanant T, Achalapong J, Sabsanong P, Chotivanich N, Winiyakul N, Ariyadej S, Kanjanasing A, Ratanakosol J, Hemvuttiphan J, Kengsakul K, Wannapira W, Sittipiyasakul V, Pornkitprasarn W, Liampongsabuddhi P, McIntosh K, Van Dyke RB, Frenkel LM, Koetsawang S, Le Coeur S, Kanchana S; PHPT-4 Study Team. Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Clin Infect Dis. 2010 Mar 15;50(6):898-908. doi: 10.1086/650745.
Results Reference
result
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One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine
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