Trial record 1 of 1 for:    NCT 00144183
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A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00144183
First received: September 2, 2005
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

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.


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: 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.)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 407
Study Start Date: January 2003
Estimated Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00144183

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
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator B.I. South Africa (Pty.) Ltd.
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

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: November 1, 2013
Health Authority: South Africa: Medicines Control Council

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Nevirapine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 19, 2014