A Study of Single Dose NVP With 4 or 7 Day Course of Combivir for pMTCT - Treatment Options Preservation Study (TOPS)
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Purpose
A study that aims to show the resistance profile that develops in previously untreated populations that are given nevirapine only and nevirapine combined with Zidovudine and 3TC for the prevention of mother to child transmission. During an interim analysis it was discovered that the nevirapine-only treated patients showed more resistance than the combination-treated patients, and thus the nevirapine only arm of the study was discontinued. The study now monitors the resistance patterns of patients given nevirapine and ZDV+3TC for 4 versus 7 days.
| Condition | Intervention | Phase |
|---|---|---|
|
Acquired Immunodeficiency Syndrome |
Drug: Nevirapine (NVP) Drug: Zidovudine (ZCV) Drug: 3TC |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | Open Label Study of Single Dose NVP With 4 vs 7 Day Course of Combivir for pMTCT - Treatment Options Preservation Study (TOPS) |
- The percentage of mothers with HIV-1 isolates with new NNRTI drug resistant mutations identified by genotypic sequencing of specimens collected within six weeks following delivery. [ Time Frame: baseline-48 weeks ]
- How many infants get HIV How many infants get HIV with resistance associated mutations How long the resistance remains [ Time Frame: baseline-48 weeks ]
| Estimated Enrollment: | 407 |
| Estimated Study Completion Date: | January 2007 |
-
Drug: Nevirapine (NVP)
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
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Contacts and Locations| South Africa | |
| Boehringer Ingelheim Investigational Site | |
| Attridgeville, South Africa, 0081 | |
| Boehringer Ingelheim Investigational Site | |
| Cape Town, South Africa, 7505 | |
| Boehringer Ingelheim Investigational Site | |
| Durban, South Africa, 4001 | |
| Boehringer Ingelheim Investigational Site | |
| Johannesburg, South Africa, 2093 | |
| Boehringer Ingelheim Investigational Site | |
| Soweto, South Africa, 2013 | |
| Study Chair: | Boehringer Ingelheim Study Coordinator | B.I. South Africa (Pty.) Ltd. |
More Information
Additional Information:
No publications provided by Boehringer Ingelheim Pharmaceuticals
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| ClinicalTrials.gov Identifier: | NCT00144183 History of Changes |
| Other Study ID Numbers: | 1100.1413, MCC;N2/19/8/2(1958) |
| Study First Received: | September 2, 2005 |
| Last Updated: | May 18, 2012 |
| Health Authority: | South Africa: Medicines Control Council |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases Zidovudine Nevirapine |
Lamivudine, zidovudine drug combination Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 21, 2013