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

This study has been completed.
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)
ClinicalTrials.gov Identifier:
NCT00074412
First received: December 11, 2003
Last updated: July 5, 2013
Last verified: July 2013
Results First Received: May 30, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Prevention
Condition: HIV Infections
Interventions: Drug: Nevirapine
Drug: Nevirapine placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
HIV-infected pregnant women were recruited from antenatal clinics at DAIDS Clinical Trials Sites in Zimbabwe, South Africa, Uganda & Tanzania between May 14, 2008 & January 20th 2010. 1700 mother/infant pairs were enrolled & infants were given daily doses of Nevirapine for 6 weeks at which point there were randomized to placebo or extended NVP.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Infants were excluded from randomization if in first 42 days: had a positive HIV-1 DNA PCR, breastfeeding was discontinued, never initiated or permanently discontinued open-label NVP, certain graded abnormal labs, skin rash grade2B or higher, clinical hepatitis, serious illness/condition that prevented compliance, or use of rifampin/ketoconazole.

Reporting Groups
  Description
Placebo For infants: extended treatment with NVP placebo
Nevirapine For infants: extended treatment with NVP

Participant Flow:   Overall Study
    Placebo   Nevirapine
STARTED   763 [1]   759 [1] 
Week 8 Visit   759   759 
Month 3 Visit   759   755 
Month 4 Visit   758   752 
Month 5 Visit   756   750 
Month 6 Visit   748   748 
Month 9 Visit   741   741 
Month 12 Visit   733   735 
COMPLETED   681 [2]   675 [2] 
NOT COMPLETED   82   84 
Death                30                26 
Lost to Follow-up                52                58 
[1] Number of infants randomized at 6 weeks.
[2] Number of infants who completed final 18 month visit: out of 733 infants who were expected.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Nevirapine For infants: extended treatment with NVP
Placebo For infants: extended treatment with NVP placebo
Total Total of all reporting groups

Baseline Measures
   Nevirapine   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 759   763   1522 
Age 
[Units: Participants]
     
<=18 years   759   763   1522 
Between 18 and 65 years   0   0   0 
>=65 years   0   0   0 
Gender, Customized 
[Units: Participants]
     
Ambiguous   1   0   1 
Male   363   398   761 
Female   395   365   760 
Region of Enrollment 
[Units: Participants]
     
Tanzania   98   99   197 
Uganda   259   261   520 
South Africa   171   171   342 
Zimbabwe   231   232   463 
Categorical Infant Birthweight (g) 
[Units: Participants]
     
Missing   0   1   1 
2000-2499   50   52   102 
2500-2999   214   211   425 
3000-3499   329   336   665 
>=3500   166   163   329 


  Outcome Measures
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1.  Primary:   HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study   [ Time Frame: At Month 6 ]

2.  Primary:   Frequency and Severity of Adverse Reactions Among Participating Infants   [ Time Frame: 6 weeks through 18 months ]
  Hide Outcome Measure 2

Measure Type Primary
Measure Title Frequency and Severity of Adverse Reactions Among Participating Infants
Measure Description 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.
Time Frame 6 weeks through 18 months  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
A total of 1519 infants, 758 in the NVP arm and 761 in the placebo arm, initiated study product and were thus included in the analysis for the frequency and severity of adverse reactions.

Reporting Groups
  Description
Nevirapine For infants: extended treatment with NVP
Placebo For infants: extended treatment with NVP placebo

Measured Values
   Nevirapine   Placebo 
Participants Analyzed 
[Units: Participants]
 758   761 
Units Analyzed (Adverse Events) 
[Units: Adverse Events]
 2014   1964 
Frequency and Severity of Adverse Reactions Among Participating Infants 
[Units: Number of Adverse Events]
   
Death   26   30 
Life-Threatening   87   87 
Severe   375   332 
Moderate   694   677 
Mild   832   838 

No statistical analysis provided for Frequency and Severity of Adverse Reactions Among Participating Infants



3.  Secondary:   Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms   [ Time Frame: At Months 6 and 18 ]

4.  Secondary:   Relative Rates of HIV Infection in the Two Arms   [ Time Frame: At Month 18 ]

5.  Secondary:   Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms   [ Time Frame: At Month 18 ]

6.  Secondary:   Frequency and Duration of Maternal Plasma and Breast Milk NVP-resistant HIV Strains and the Relationship With HIV Transmission   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Secondary:   Relationship Between Maternal Plasma and Breast Milk RNA Levels and the Risk of MTCT   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Secondary:   Frequency and Duration of NVP-resistant HIV Strains in Plasma of HIV-infected Infants   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

9.  Secondary:   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 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

10.  Secondary:   NVP Concentrations in Infants Determined to be HIV-infected and in a Sample of HIV-uninfected Infants   [ Time Frame: Week 8 and Month 3 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The rate of maternal highly active antiretroviral therapy use was higher than expected in our study. Thus there were fewer infant infections which decreased the power to detect differences in HIV transmission risks between study groups.


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