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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
  Show All Outcome Measures

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 ]

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
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Time Frame Regardless of seriousness, severity or relatedness all AEs occurring in infants after enrollment (birth) and throughout the duration of the study (18 months) must be recorded.
Additional Description Non-serious adverse events occurring in an infant between randomization and 8 months of life will be collected on a case report form. Further, Serious AEs and AEs that meet the DAIDS expedited reporting criteria will be reported through case report forms throughout the entire 18 month follow-up period.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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

Other Adverse Events
    Nevirapine   Placebo
Total, other (not including serious) adverse events     
# participants affected / at risk   614/758 (81.00%)   618/761 (81.21%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   42/758 (5.54%)   51/761 (6.70%) 
# events   48   55 
Eye disorders     
Conjunctivitis † 1     
# participants affected / at risk   62/758 (8.18%)   43/761 (5.65%) 
# events   66   53 
Gastrointestinal disorders     
Diarrhoea † 1     
# participants affected / at risk   57/758 (7.52%)   55/761 (7.23%) 
# events   63   65 
Infections and infestations     
Conjunctivitis bacterial † 1     
# participants affected / at risk   76/758 (10.03%)   72/761 (9.46%) 
# events   86   80 
Gastroenteritis † 1     
# participants affected / at risk   188/758 (24.80%)   208/761 (27.33%) 
# events   268   288 
Malaria † 1     
# participants affected / at risk   122/758 (16.09%)   112/761 (14.72%) 
# events   164   160 
Oral candidiasis † 1     
# participants affected / at risk   97/758 (12.80%)   79/761 (10.38%) 
# events   121   93 
Upper respiratory infection † 1     
# participants affected / at risk   135/758 (17.81%)   187/761 (24.57%) 
# events   159   223 
Investigations     
Haemoglobin decreased † 1     
# participants affected / at risk   73/758 (9.63%)   64/761 (8.41%) 
# events   76   67 
Neutrophil count decreased † 1     
# participants affected / at risk   145/758 (19.13%)   121/761 (15.90%) 
# events   181   153 
Skin and subcutaneous tissue disorders     
Dermatitis atopic † 1     
# participants affected / at risk   55/758 (7.26%)   37/761 (4.86%) 
# events   60   44 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (14.1)



  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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Statistical Research Associate
Organization: Statistical Center for HIV/AIDS Research and Prevention
phone: 2066677524
e-mail: cherron@fhcrc.org


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00074412     History of Changes
Other Study ID Numbers: HPTN 046
10142 ( Registry Identifier: DAIDS ES )
Study First Received: December 11, 2003
Results First Received: May 30, 2013
Last Updated: July 5, 2013
Health Authority: United States: Food and Drug Administration