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

Information source: Institut de Recherche pour le Developpement
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Zidovudine (ZDV) (Drug); Didanosine (ddI) (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Institut de Recherche pour le Developpement

Official(s) and/or principal investigator(s):
Marc Lallemant, MD, Principal Investigator, Affiliation: Institut de Recherche pour le Developpement

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.

Clinical Details

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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: 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

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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.)

Locations and Contacts

Bhumibol Adulyadej Hospital, Bangkok 10220, Thailand

Health Promotion Hospital Regional Center I, Bangkok 10220, Thailand

Somdej Pranangchao Sirikit Hospital, Chonburi 20180, Thailand

Samutprakarn Hospital, Samutprakarn 10280, Thailand

Chacheongsao Hospital, Muang, Chacheongsao 24000, Thailand

Prapokklao Hospital, Muang, Chantaburi 22000, Thailand

Nakornping Hospital, Mae Rim, Chiang Mai 50180, Thailand

Health Promotion Center Region 10, Muang, Chiang Mai 50100, Thailand

Lamphun Hospital, Munag, Chiang Mai 51000, Thailand

Mae Chan Hospital, Mae Chan, Chiang Rai 57110, Thailand

Mae Sai Hospital, Mae Sai, Chiang Rai 57130, Thailand

Phan Hospital, Phan, Chiang Rai 57120, Thailand

Chiangrai Prachanukroh Hospital, Muang, Chiangrai 57000, Thailand

Chonburi Hospital, Muang, Chonburi 20000, Thailand

Kalasin Hospital, Muang, Kalasin 46000, Thailand

Phaholpolphayuhasena Hospital, Munag, Kanjanaburi 71000, Thailand

Kranuan Crown Prince Hospital, Kranuan, Khon Kaen 40170, Thailand

Khon Kaen Hospital, Muang, Khon Kaen 40000, Thailand

Regional Health Promotion Centre 6, Khon Kaen, Muang, Khon Kaen 40000, Thailand

Srinagarind Hospital, Muang, Khon Kaen 40002, Thailand

Lampang Hospital, Muang, Lampang 52000, Thailand

Nakhonpathom Hospital, Muang, Nakhonpathom 73000, Thailand

Maharaj Nakornratchasrima Hospital, Muang, Nakornratchasrima 30000, Thailand

Nong Khai Hospital, Muang, Nong Kai 43000, Thailand

Pranangklao Hospital, Muang, Nonthaburi 11000, Thailand

Chiang Kham Hospital, Chiang Kham, Phayao 56110, Thailand

Buddhachinaraj Hospital, Muang, Pitsanuloke 65000, Thailand

Ratchaburi Hospital, Muang, Ratchaburi 70000, Thailand

Rayong Hospital, Muang, Rayong 21000, Thailand

Roi-et Hospital, Muang, Roi-et 45000, Thailand

Samutsakorn Hospital, Muang, Samutsakorn 74000, Thailand

Hat Yai Hospital, Hat Yai, Songkla 90110, Thailand

Additional Information

Related publications:

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. Epub 2004 Jul 9.

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. Epub 2004 Jul 9.

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.

Starting date: December 2004
Last updated: January 4, 2012

Page last updated: August 23, 2015

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