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Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding

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ClinicalTrials.gov Identifier: NCT00074412
Recruitment Status : Completed
First Posted : December 15, 2003
Results First Posted : September 16, 2013
Last Update Posted : September 16, 2013
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE December 11, 2003
First Posted Date  ICMJE December 15, 2003
Results First Submitted Date  ICMJE May 30, 2013
Results First Posted Date  ICMJE September 16, 2013
Last Update Posted Date September 16, 2013
Study Start Date  ICMJE January 2007
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2013)
  • HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study [ Time Frame: At Month 6 ]
  • Frequency and Severity of Adverse Reactions Among Participating Infants [ Time Frame: 6 weeks through 18 months ]
    For those infants who were randomized at 6 weeks and who initiated study drug we looked at the frequency and severity of adverse reactions through 18 months of study. The severity of all AEs was graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. The term severity is described as the intensity grade or level for specific event (i.e. mild, moderate, severe, or life-threatening). Severity is not the same as seriousness.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00074412 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2013)
  • Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms [ Time Frame: At Months 6 and 18 ]
  • Relative Rates of HIV Infection in the Two Arms [ Time Frame: At Month 18 ]
  • Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms [ Time Frame: At Month 18 ]
  • Frequency and Duration of Maternal Plasma and Breast Milk NVP-resistant HIV Strains and the Relationship With HIV Transmission [ Time Frame: Throughout study ]
  • Relationship Between Maternal Plasma and Breast Milk RNA Levels and the Risk of MTCT [ Time Frame: Throughout study ]
  • Frequency and Duration of NVP-resistant HIV Strains in Plasma of HIV-infected Infants [ Time Frame: Throughout study ]
  • Rates of Disease Progression as Defined by CD4 Counts, HIV-1 RNA PCR, and Mortality in Infected Infants in the Two Arms [ Time Frame: Throughout study ]
  • NVP Concentrations in Infants Determined to be HIV-infected and in a Sample of HIV-uninfected Infants [ Time Frame: Week 8 and Month 3 ]
    Samples for NVP concentration were selected from the Version 3.0 infants who were randomized to NVP at 6 weeks and whose mothers were not on 3 or more antiretrovirals at the time of randomization. All infants HIV-infected by 6 months who met this criteria were selected and matched to HIV-uninfected infants who also met this criteria in a 1:3 ratio. NVP concentrations were measured by high liquid chromatographic/mass spectroscopy from the aforementioned infants plasma samples collected at week 8 and month 3. Median NVP concentrations were compared
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding
Official Title  ICMJE A Phase III Trial to Determine the Efficacy and Safety of an Extended Regimen of Nevirapine in Infants Born to HIV-Infected Women to Prevent Vertical HIV Transmission During Breastfeeding
Brief Summary The many benefits of breastfeeding are well documented. However, because of the risk of mother-to-child transmission (MTCT) of HIV from an HIV infected mother to her infant, there is considerable concern over the practice, especially in developing countries. The purpose of this study is to determine the safety and effectiveness of the anti-HIV drug nevirapine (NVP) in preventing MTCT of HIV in breastfeeding infants born to HIV infected women in South Africa, Tanzania, Uganda, and Zimbabwe.
Detailed Description

Breastfeeding provides general health, growth, and development benefits to an infant and significantly decreases the risk of certain acute and chronic diseases. Breastfeeding also decreases financial burden on the mother by decreasing the need for infant formula and health care for the infant. However, clinical evidence has shown that HIV can be readily transmitted through breast milk, although the risk of HIV MTCT over time while breastfeeding has been difficult to determine. Given the many advantages of breastfeeding and the significant obstacles to substituting formula for breast milk in developing countries, there is an urgent need to make breastfeeding by HIV infected women safe. This study will evaluate the safety and efficacy of an extended NVP regimen for prevention of MTCT of HIV through breastfeeding.

This study will last approximately 3.5 years. Mother/infant pairs will be enrolled over a period of 18 to 24 months. During the third trimester of pregnancy, HIV infected participants will receive HIV counseling and the intrapartum/neonatal two-dose NVP prophylaxis regimen to prevent MTCT. Mothers will also be given infant feeding options counseling and information on administering the study drug to the infant. Infants who were randomly assigned to receive a placebo and older than 6 weeks of age as of 08/10/07 OR to receive NVP will continue their treatment assignment. Infants who were randomly assigned to receive a placebo and are 6 weeks of age or less as of 08/10/07 will receive open-label NVP through Day 42 of life. For all other participants, all randomized infants will receive extended NVP through 6 weeks (Day 42) of life. All eligible infants will be randomly assigned to one of two groups at Week 6 following birth. The first group will receive extended NVP treatment; the second group will receive nevirapine placebo. Randomized infants will receive the extended NVP or NVP placebo through the first 6 months of life or until cessation of breastfeeding, whichever occurs earlier. Mothers will be instructed to begin giving their infants their assigned intervention starting at Day 3 to Day 7 postpartum. All mothers and infants outside of the study will be offered the local standard of care antiretroviral (ARV) regimen for the prevention of MTCT, but these ARVs will not be provided by the study.

Follow-up evaluations will be conducted at Weeks 2 and 6 and Months 3, 6, 12, and 18 for mothers, and at Weeks 2, 5, 6, and 8 and Months 3, 4, 5, 6, 9, 12, and 18 for infants. Study visits will include physical examinations, blood tests (including HIV tests), and medical histories. Study participants will be followed for up to 3.5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Nevirapine
    10 mg/ml oral suspension taken once daily up to 6 months of age. Dosage will increase throughout study.
    Other Name: NVP
  • Drug: Nevirapine placebo
    Oral suspension taken once daily up to 6 months of age
    Other Name: NVP placebo
Study Arms  ICMJE
  • Experimental: 2A
    For infants: extended treatment with NVP
    Intervention: Drug: Nevirapine
  • Placebo Comparator: 2B
    For infants: extended treatment with NVP placebo
    Intervention: Drug: Nevirapine placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2013)
2026
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
1576
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Note: As of 08/10/07, the arm assignments for current and new participants have changed. Please see the above description for this trial for more information.

Inclusion Criteria for Mothers:

  • 18 years of age or older
  • HIV infected
  • In third trimester of pregnancy, or at most 3 days post-delivery
  • If baby is not yet born, planning to deliver at a facility where the study is being conducted
  • Plan to breastfeed

Exclusion Criteria for Mothers:

  • Complications with this pregnancy
  • Serious medical condition that would interfere with the study (e.g., that would prevent breastfeeding or adherence to the follow-up schedule), as judged by the on-site clinician

Inclusion Criteria for Infants:

  • Born to an HIV infected mother who is eligible for the study
  • Weighed at least 2000 grams (4.4 lbs) at birth
  • Blood sample obtained from the infant for HIV-1 DNA PCR, CBC with differential, and ALT
  • Infants in a multiple birth are eligible only if both/all infants are eligible for the study and assigned to the same study group
  • Able to breastfeed (e.g., mother and infant alive with no condition apparent that would prevent breastfeeding)

Exclusion Criteria for Infants:

  • HIV DNA PCR positive at birth
  • ALT of Grade 2 or higher at birth
  • Hemoglobin, absolute neutrophil count, or platelet count of Grade 3 or higher at birth
  • Skin rash of Grade 2B (urticaria), Grade 3, or above
  • Confirmed or suspected clinical hepatitis
  • Serious illness or condition that would interfere with compliance with study procedures
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa,   Tanzania,   Uganda,   Zimbabwe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00074412
Other Study ID Numbers  ICMJE HPTN 046
10142 ( Registry Identifier: DAIDS ES )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • National Institute on Drug Abuse (NIDA)
  • National Institute of Mental Health (NIMH)
Investigators  ICMJE
Study Chair: Hoosen M. Coovadia, MD, MBBS Centre for HIV Networking (HIVAN), Nelson Mandela School of Medicine, University of Natal
Study Chair: Laura Guay, MD Johns Hopkins University
Study Chair: Wafaie Fawzi, MD, PhD Department of Nutrition, Harvard School of Public Health
Study Chair: Yvonne Maldonado, MD Stanford University
Study Chair: Daya Moodley, MSc, PhD Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of Natal
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP