Acquired Immunodeficiency SyndromePhase 3NCT00144183
A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
A Phase 3 study testing Nevirapine (NVP), Zidovudine (ZCV) and 3TC in people with Acquired Immunodeficiency Syndrome, run by Boehringer Ingelheim at 5 sites in South Africa.
Trial summary
To determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir®, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Acquired Immunodeficiency Syndrome
- What is being tested?
- Nevirapine (NVP), Zidovudine (ZCV) and 3TC
- Type of treatment
- Pill or oral medicine
- How many people
- 407 participants
- Where
- 5 sitesSouth Africa
- Study dates
- Jan 2003to Jan 2007
- Phase
- Phase 3
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pregnant women identified at antenatal clinics after from 34 weeks gestation and who are antiretroviral drug naive.
- Mothers with a documented positive HIV Rapid test confirmed by a detectable HI V-1 RNA PCR (viral load).
- Mother to have a screening viral load of > 2000 RNA copies/mL.
Who cannot join
- Mothers who, in the opinion of the investigator ,cannot be relied on to return with their infants for postnatal visits.
- Mothers who have received any antiretroviral drugs previously.
- Clinical suspicion of intra-uterine foetal death
- Unwillingness or inability to reasonably comply with the protocol requirements.
- Use of any other investigational product during the pregnancy and for the dura tion of the study period.
- Patients with a recent history of pancreatitis or peripheral neuropathy.
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- Patients with renal failure requiring dialysis.
- Patients with evidence of hepatic dysfunction as measured by total bilirubin > 2.5 times ULN or AST/ALT > 5 times ULN at the screening visit.
- Patients with any one of the following additional laboratory abnormalities at screening : Haemoglobin concentration < 7.5 g/dl. Neutrophil count < 750 cells/mm3. Platelet count < 75,000 cells/mm3. Serum amylase > 2 x ULN.
- recent history ( during the pregnancy) of drug abuse or alcoholism.
- Mothers who will undergo elective caesarean section.
- If known prior to delivery, mothers with foetuses with anomalies incompatible with life.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
South Africa5 sites
Boehringer Ingelheim Investigational Site
Attridgeville, 0081
Boehringer Ingelheim Investigational Site
Cape Town, 7505
Boehringer Ingelheim Investigational Site
Durban, 4001
Boehringer Ingelheim Investigational Site
Johannesburg, 2093
Boehringer Ingelheim Investigational Site
Soweto, 2013
About this study
Official title: An Open-label Study Evaluating the Resistance Profile of Single Dose Nevirapine(NVP) When Combined With a 4 or 7 Day Course of Combivir® (ZDV/3TC) Compared to Single Dose Nevirapine for the Prevention of Mother to Child Transmission (pMTCT) of HIV - Treatment Options Preservation Study (T.O.P.S.)
To determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir®, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
Read the detailed description
An open-label, randomised, multicentre study to determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
An interim analysis of the first 61 patients showed that a clinical and statistical difference exists between the occurrence of HIV-1 NNRTI resistant mutations in the single dose nevirapine only arm (50%) and the two other combination arms (9%). These findings partially answered the objectives outlined in the initial objectives. Consequently enrolment onto the single dose nevirapine arm was terminated. The objective of the trial was modified to compare whether either the 4 or the 7 day combination of ZDV+3TC and nevirapine would result in any significant reduction in the incidence of nevirapine resistance.
Study Hypothesis:
Evaluations of HIV-1 resistance patterns in trials of pMTCT have demonstrated nevirapine resistant HIV-1 isolates in approximately 15-20% of mothers 4-6 weeks after receiving either a single or two dose 200mg nevirapine regimen. Although the ability to detect these genotypic mutations decreases to 0% by about 18 months, it is not clear whether this resistance is clinically significant.(HIVNET 012).
Empirically then it would seem useful to develop a strategy to diminish the emergence of this early resistance, therefore this study is proposed to evaluate whether the effect of 4 or 7 days of 3TC+ ZDV added to a single dose nevirapine regimen for the prevention of MTCT will prevent the emergence of resistance to nevirapine.
Comparison(s):
ACTG 076, Thai, PETRA , HIVNET 006/012, SAINT
- Conditions
- Acquired Immunodeficiency Syndrome
- Being tested
- Nevirapine (NVP), Zidovudine (ZCV), 3TC
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nevirapine (NVP)Drug
Nevirapine 200mg once daily for 14 days followed by 200mg twice daily thereafter for the remainder of the treatment period. Combivir®, one tablet twice daily.
Zidovudine (ZCV)Drug
3TCDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing
Measured: 6 weeks following delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startJan 2003
- Primary completionJan 2007
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 407 participants
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Boehringer Ingelheim Study Coordinator, Study chair, B.I. South Africa (Pty.) Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00144183
- Sponsor's protocol ID
- 1100.1413
- Other IDs
- MCC;N2/19/8/2(1958)
- Status last verified
- Nov 2013
- First submitted
- 2 Sep 2005
- Last updated
- 4 Nov 2013
- Results posted
- No
Publications
McIntyre JA, Hopley M, Moodley D, Eklund M, Gray GE, Hall DB, Robinson P, Mayers D, Martinson NA. Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: a randomized clinical trial. PLoS Med. 2009 Oct;6(10):e1000172. doi: 10.1371/journal.pmed.1000172. Epub 2009 Oct 27.
PubMed 19859531
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study Evaluating the Resistance Profile of Single Dose Nevirapine(NVP) When Combined With a 4 or 7 Day Course of Combivir® (ZDV/3TC) Compared to Single Dose Nevirapine for the Prevention of Mother to Child Transmission (pMTCT) of HIV - Treatment Options Preservation Study (T.O.P.S.)
- ClinicalTrials.gov ID
- NCT00144183
- Acronym / sponsor ID
- 1100.1413
- Conditions
- Acquired Immunodeficiency Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 407 participants
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jan 2003
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007
- First posted
- 5 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.
To determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir®, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
Detailed description
An open-label, randomised, multicentre study to determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
An interim analysis of the first 61 patients showed that a clinical and statistical difference exists between the occurrence of HIV-1 NNRTI resistant mutations in the single dose nevirapine only arm (50%) and the two other combination arms (9%). These findings partially answered the objectives outlined in the initial objectives. Consequently enrolment onto the single dose nevirapine arm was terminated. The objective of the trial was modified to compare whether either the 4 or the 7 day combination of ZDV+3TC and nevirapine would result in any significant reduction in the incidence of nevirapine resistance.
Study Hypothesis:
Evaluations of HIV-1 resistance patterns in trials of pMTCT have demonstrated nevirapine resistant HIV-1 isolates in approximately 15-20% of mothers 4-6 weeks after receiving either a single or two dose 200mg nevirapine regimen. Although the ability to detect these genotypic mutations decreases to 0% by about 18 months, it is not clear whether this resistance is clinically significant.(HIVNET 012).
Empirically then it would seem useful to develop a strategy to diminish the emergence of this early resistance, therefore this study is proposed to evaluate whether the effect of 4 or 7 days of 3TC+ ZDV added to a single dose nevirapine regimen for the prevention of MTCT will prevent the emergence of resistance to nevirapine.
Comparison(s):
ACTG 076, Thai, PETRA , HIVNET 006/012, SAINT
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Pregnant women identified at antenatal clinics after from 34 weeks gestation and who are antiretroviral drug naive.
- Mothers with a documented positive HIV Rapid test confirmed by a detectable HI V-1 RNA PCR (viral load).
- Mother to have a screening viral load of > 2000 RNA copies/mL.
Key exclusion criteria (12 listed)
- Mothers who, in the opinion of the investigator ,cannot be relied on to return with their infants for postnatal visits.
- Mothers who have received any antiretroviral drugs previously.
- Clinical suspicion of intra-uterine foetal death
- Unwillingness or inability to reasonably comply with the protocol requirements.
- Use of any other investigational product during the pregnancy and for the dura tion of the study period.
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 |
|---|---|---|
| Nevirapine (NVP)Nevirapine 200mg once daily for 14 days followed by 200mg twice daily thereafter for the remainder of the treatment period. Combivir®, one tablet twice daily. | Drug | – |
| Zidovudine (ZCV) | Drug | – |
| 3TC | Drug | – |
Primary outcome
Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing
Time frame: 6 weeks following delivery
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 4 Nov 2013.
- Derived from this study: PubMed 19859531McIntyre JA, Hopley M, Moodley D, Eklund M, Gray GE, Hall DB, Robinson P, Mayers D, Martinson NA. Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: a randomized clinical trial. PLoS Med. 2009 Oct;6(10):e1000172. doi: 10.1371/journal.pmed.1000172. Epub 2009 Oct 27.
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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.
Boehringer Ingelheim Study Coordinator study chair
B.I. South Africa (Pty.) Ltd.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nevirapine (NVP), Zidovudine (ZCV) and 3TC in people with Acquired Immunodeficiency Syndrome, run by Boehringer Ingelheim at 5 sites in South Africa.
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 3 inclusion and 12 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 4 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in South Africa. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing (time frame: 6 weeks following delivery). 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 NCT00144183, which also lists 1 linked publication.
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 4 Nov 2013.