A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)

November 1, 2013 updated by: Boehringer Ingelheim

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment

407

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
      • 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
        • Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
6 weeks following delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

January 1, 2007

Study Completion

January 1, 2007

Study Registration Dates

First Submitted

September 2, 2005

First Submitted That Met QC Criteria

September 2, 2005

First Posted (Estimate)

September 5, 2005

Study Record Updates

Last Update Posted (Estimate)

November 3, 2013

Last Update Submitted That Met QC Criteria

November 1, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1100.1413
  • MCC;N2/19/8/2(1958)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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