HIVPhase 2TD-2NCT00204308
Maternal TDF and FTC to Reduce NNRTI Resistance Mutations After Intrapartum NVP
A Phase 2 study testing Combination tenofovir-emtricitabine in people with HIV and Pregnancy, run by University of North Carolina, Chapel Hill at 2 sites in Zambia.
Trial summary
The purpose of this study is to determine whether the addition of tenofovir (TDF) and emtricitabine (FTC)to a standard PMTCT regimen containing single-dose nevirapine (NVP) can reduce the development of post-ingestion HIV resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Read more about this study
- Who is it for?
- Ages 16 years and older, women only
- What is being tested?
- Combination tenofovir-emtricitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 2 sitesZambia
- Study dates
- Mar 2005to May 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Serologically confirmed HIV infection;
- Gestational age of 28 to 38 weeks;
- Previous selection of a NVP-based PMTCT regimen (with or without ZDV)
- Willingness to participate in a randomized trial;
- Willingness to follow up in a postpartum visit schedule;
- Willingness to allow her infant to participate in this trial;
Who cannot join
- Use of antiretroviral medications before this pregnancy, even in a single dose.
- Current use of antiretroviral medications for treatment of advanced HIV disease and/or AIDS
- Illness or complication of pregnancy likely to warrant transfer to the University Teaching Hospital (UTH), known at time of randomization;
- Known or suspected allergy to NVP or other benzodiazepine medications;
- History of known liver disease.
- Hemoglobin level of 7.9 g/dL or less
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: Addition of Single-dose, Maternal Tenofovir and Emtricitabine to Reduce Non-nucleoside Reverse Transcriptase Inhibitor Resistance Mutations in the Setting of Zidovudine and Nevirapine for Prevention of Mother-to-child HIV Transmission
The purpose of this study is to determine whether the addition of tenofovir (TDF) and emtricitabine (FTC)to a standard PMTCT regimen containing single-dose nevirapine (NVP) can reduce the development of post-ingestion HIV resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Read the detailed description
Single-dose intrapartum and neonatal nevirapine (NVP), either alone or in combination with short course zidovudine (ZDV) is in widespread use to prevent mother-to-child HIV transmission throughout the developing world. Though the public health benefits cannot be overstated, widespread use of NVP in this fashion may come at a cost. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are induced in at least 20% and probably a larger proportion of women exposed to NVP in this fashion. Addition of short-course ZDV does not appear to mitigate this effect substantially. The full implications of these NVP resistance mutations are yet unknown, though there is concern that they may result in reduced efficacy of the NVP or other NNRTIs in long-term, therapeutic regimens.
We are conducting a clinical trial of tenofovir (TDF) and emtricitabine (FTC), marketed as a fixed dose combination, Truvada ™, to reduce NNRTI-resistance post-delivery in the setting of NVP with or without ZDV for PMTCT. TDF and FTC are both Category B drugs and are approved for use in pregnancy. They have several characteristics that make them ideal candidate drugs for use in conjunction with NVP, including long intracellular half-lives and established safety profile among adults for HIV treatment.
Women will be enrolled between 28 and 38 weeks of gestation. As part of normal PMTCT services, they may choose NVP-boosted ZDV or single dose NVP for PMTCT; We anticipate that most (~80%) will choose the former. At arrival for delivery, they will be randomized to receive either the two study drugs (intervention) or no drug (control). A total of 400 women will be randomized, and followed, along with their infants, for 6 months.
- Being tested
- Combination tenofovir-emtricitabine
- Keywords
- HIV, Pregnancy, Mother-to-child transmission of HIV, Drug resistance, Nevirapine resistance, NNRTI resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination tenofovir-emtricitabineDrug
Also called Truvada
Tenofovir disoproxil 300 mg / emtricitabine 200 mg taken as a single dose during labor
| Study group | Role | What they receive |
|---|---|---|
| combination tenofovir-emtricitabine | Experimental | Not described Receives: Drug: Combination tenofovir-emtricitabine |
| control arm | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors
Measured: 6 weeks
Secondary outcomes (2)
maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors
Measured: 2 weeks
maternal hematological and renal function after TDF-FTC use
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startMar 2005
- Primary completionMay 2007
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Elizabeth Glaser Pediatric AIDS Foundation
- Responsible party
- Principal investigator, Benjamin Chi, MD, MSc, University of North Carolina, Chapel Hill
- Investigators
- Jeffrey S A Stringer, MD, Principal investigator, University of Alabama at BirminghamBenjamin H Chi, MD, Study director, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00204308
- Sponsor's protocol ID
- EGSA 19-02
- Acronym
- TD-2
- Status last verified
- May 2012
- First submitted
- 12 Sep 2005
- Last updated
- 31 May 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chi BH, Sinkala M, Mbewe F, Cantrell RA, Kruse G, Chintu N, Aldrovandi GM, Stringer EM, Kankasa C, Safrit JT, Stringer JS. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. Lancet. 2007 Nov 17;370(9600):1698-705. doi: 10.1016/S0140-6736(07)61605-5. Epub 2007 Nov 7.
PubMed 17997151Chi BH, Chintu N, Cantrell RA, Kankasa C, Kruse G, Mbewe F, Sinkala M, Smith PJ, Stringer EM, Stringer JS. Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission. J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):220-3. doi: 10.1097/QAI.0b013e3181743969.
PubMed 18520682Chi BH, Ellis GM, Chintu N, Cantrell RA, Sinkala M, Aldrovandi GM, Warrier R, Mbewe F, Nakamura K, Stringer EM, Frenkel LM, Stringer JS. Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1099-106. doi: 10.1089/aid.2009.0088.
PubMed 19886836Dorton BJ, Mulindwa J, Li MS, Chintu NT, Chibwesha CJ, Mbewe F, Frenkel LM, Stringer JS, Chi BH. CD4+ cell count and risk for antiretroviral drug resistance among women using peripartum nevirapine for perinatal HIV prevention. BJOG. 2011 Mar;118(4):495-9. doi: 10.1111/j.1471-0528.2010.02835.x. Epub 2010 Dec 24.
PubMed 21199294
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Single-dose, Maternal Tenofovir and Emtricitabine to Reduce Non-nucleoside Reverse Transcriptase Inhibitor Resistance Mutations in the Setting of Zidovudine and Nevirapine for Prevention of Mother-to-child HIV Transmission
- ClinicalTrials.gov ID
- NCT00204308
- Acronym / sponsor ID
- TD-2 / EGSA 19-02
- Keywords
- HIV, Pregnancy, Mother-to-child transmission of HIV, Drug resistance, Nevirapine resistance, NNRTI resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Elizabeth Glaser Pediatric AIDS Foundation
- Study start
- Mar 2005
- Primary completion
- May 2007 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the addition of tenofovir (TDF) and emtricitabine (FTC)to a standard PMTCT regimen containing single-dose nevirapine (NVP) can reduce the development of post-ingestion HIV resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Detailed description
Single-dose intrapartum and neonatal nevirapine (NVP), either alone or in combination with short course zidovudine (ZDV) is in widespread use to prevent mother-to-child HIV transmission throughout the developing world. Though the public health benefits cannot be overstated, widespread use of NVP in this fashion may come at a cost. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are induced in at least 20% and probably a larger proportion of women exposed to NVP in this fashion. Addition of short-course ZDV does not appear to mitigate this effect substantially. The full implications of these NVP resistance mutations are yet unknown, though there is concern that they may result in reduced efficacy of the NVP or other NNRTIs in long-term, therapeutic regimens.
We are conducting a clinical trial of tenofovir (TDF) and emtricitabine (FTC), marketed as a fixed dose combination, Truvada ™, to reduce NNRTI-resistance post-delivery in the setting of NVP with or without ZDV for PMTCT. TDF and FTC are both Category B drugs and are approved for use in pregnancy. They have several characteristics that make them ideal candidate drugs for use in conjunction with NVP, including long intracellular half-lives and established safety profile among adults for HIV treatment.
Women will be enrolled between 28 and 38 weeks of gestation. As part of normal PMTCT services, they may choose NVP-boosted ZDV or single dose NVP for PMTCT; We anticipate that most (~80%) will choose the former. At arrival for delivery, they will be randomized to receive either the two study drugs (intervention) or no drug (control). A total of 400 women will be randomized, and followed, along with their infants, for 6 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| combination tenofovir-emtricitabine | Experimental | Drug: Combination tenofovir-emtricitabine |
| control arm | No intervention | – |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Serologically confirmed HIV infection;
- Gestational age of 28 to 38 weeks;
- Previous selection of a NVP-based PMTCT regimen (with or without ZDV)
- Willingness to participate in a randomized trial;
- Willingness to follow up in a postpartum visit schedule;
Key exclusion criteria (6 listed)
- Use of antiretroviral medications before this pregnancy, even in a single dose.
- Current use of antiretroviral medications for treatment of advanced HIV disease and/or AIDS
- Illness or complication of pregnancy likely to warrant transfer to the University Teaching Hospital (UTH), known at time of randomization;
- Known or suspected allergy to NVP or other benzodiazepine medications;
- History of known liver disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination tenofovir-emtricitabineAlso: TruvadaTenofovir disoproxil 300 mg / emtricitabine 200 mg taken as a single dose during labor | Drug | combination tenofovir-emtricitabine |
Primary outcome
maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors
Time frame: 6 weeks
2 secondary outcomes
maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors
Time frame: 2 weeks
maternal hematological and renal function after TDF-FTC use
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2012.
- Results publication: PubMed 17997151Chi BH, Sinkala M, Mbewe F, Cantrell RA, Kruse G, Chintu N, Aldrovandi GM, Stringer EM, Kankasa C, Safrit JT, Stringer JS. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial. Lancet. 2007 Nov 17;370(9600):1698-705. doi: 10.1016/S0140-6736(07)61605-5. Epub 2007 Nov 7.
- Results publication: PubMed 18520682Chi BH, Chintu N, Cantrell RA, Kankasa C, Kruse G, Mbewe F, Sinkala M, Smith PJ, Stringer EM, Stringer JS. Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission. J Acquir Immune Defic Syndr. 2008 Jun 1;48(2):220-3. doi: 10.1097/QAI.0b013e3181743969.
- Results publication: PubMed 19886836Chi BH, Ellis GM, Chintu N, Cantrell RA, Sinkala M, Aldrovandi GM, Warrier R, Mbewe F, Nakamura K, Stringer EM, Frenkel LM, Stringer JS. Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1099-106. doi: 10.1089/aid.2009.0088.
- Results publication: PubMed 21199294Dorton BJ, Mulindwa J, Li MS, Chintu NT, Chibwesha CJ, Mbewe F, Frenkel LM, Stringer JS, Chi BH. CD4+ cell count and risk for antiretroviral drug resistance among women using peripartum nevirapine for perinatal HIV prevention. BJOG. 2011 Mar;118(4):495-9. doi: 10.1111/j.1471-0528.2010.02835.x. Epub 2010 Dec 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey S A Stringer, MD principal investigator
University of Alabama at Birmingham
Benjamin H Chi, MD study director
University of Alabama at Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination tenofovir-emtricitabine in people with HIV and Pregnancy, run by University of North Carolina, Chapel Hill at 2 sites in Zambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
maternal antiretroviral drug resistance to non-nucloeoside reverse transcriptase inhibitors (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00204308, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2012.