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

This study has been completed.
Sponsor:
Collaborators:
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  
Number of Participants  
[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
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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.

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

Serious Adverse Events
    Nevirapine     Placebo  
Total, serious adverse events      
# participants affected / at risk     152/758 (20.05%)     141/761 (18.53%)  
Blood and lymphatic system disorders      
Aneamia † 1    
# participants affected / at risk     1/758 (0.13%)     4/761 (0.53%)  
# events     1     4  
Cardiac disorders      
Cardipulmonary failure † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Congenital, familial and genetic disorders      
Cerebral palsy † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Congenital absence of bile ducts † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Sickle cell anaemia † 1    
# participants affected / at risk     3/758 (0.40%)     2/761 (0.26%)  
# events     4     2  
Sickle cell anaemia with crisis † 1    
# participants affected / at risk     1/758 (0.13%)     1/761 (0.13%)  
# events     1     1  
Eye disorders      
Blindness † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     6/758 (0.79%)     5/761 (0.66%)  
# events     6     5  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Inguinal hernia † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Intussusception † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Vomiting † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
General disorders      
Death † 1    
# participants affected / at risk     4/758 (0.53%)     2/761 (0.26%)  
# events     4     2  
Oedema † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Pyrexia † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Sudden infant death syndrome † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Hepatobiliary disorders      
Hyperbilirubinaemia † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Immune system disorders      
Anaphylactic reaction † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Infections and infestations      
Abscess † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Abscess bacterial † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Arthritis bacterial † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Bacteraemia † 1    
# participants affected / at risk     1/758 (0.13%)     1/761 (0.13%)  
# events     1     1  
Bronchiolitis † 1    
# participants affected / at risk     2/758 (0.26%)     4/761 (0.53%)  
# events     2     7  
Bronchopneumonia † 1    
# participants affected / at risk     18/758 (2.37%)     20/761 (2.63%)  
# events     19     23  
Cellulitis † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Cerebral malaria † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     2     0  
Febrile infection † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Gastroenteritis † 1    
# participants affected / at risk     45/758 (5.94%)     50/761 (6.57%)  
# events     50     58  
Gastroenteritis shigella † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Giardiasis † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     2  
Injection site abscess † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Lobar pneumonia † 1    
# participants affected / at risk     3/758 (0.40%)     0/761 (0.00%)  
# events     3     0  
Lower respiratory tract infection † 1    
# participants affected / at risk     6/758 (0.79%)     1/761 (0.13%)  
# events     6     2  
Malaria † 1    
# participants affected / at risk     42/758 (5.54%)     34/761 (4.47%)  
# events     50     40  
Measles † 1    
# participants affected / at risk     3/758 (0.40%)     3/761 (0.39%)  
# events     3     3  
Meningitis † 1    
# participants affected / at risk     2/758 (0.26%)     3/761 (0.39%)  
# events     2     3  
Meningitis bacterial † 1    
# participants affected / at risk     3/758 (0.40%)     0/761 (0.00%)  
# events     3     0  
Pericarditis tuberculous † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Plasmodium falciparum infection † 1    
# participants affected / at risk     1/758 (0.13%)     1/761 (0.13%)  
# events     1     1  
Pneumocystis jiroveci pneumonia † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Pneumonia † 1    
# participants affected / at risk     20/758 (2.64%)     29/761 (3.81%)  
# events     21     29  
Pneumonia bacterial † 1    
# participants affected / at risk     2/758 (0.26%)     2/761 (0.26%)  
# events     2     2  
Pulmonary tuberculosis † 1    
# participants affected / at risk     2/758 (0.26%)     2/761 (0.26%)  
# events     2     2  
Respiratory tract infection † 1    
# participants affected / at risk     2/758 (0.26%)     0/761 (0.00%)  
# events     2     0  
Sepsis † 1    
# participants affected / at risk     5/758 (0.66%)     9/761 (1.18%)  
# events     5     12  
Sepsis neonatal † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Tonsilitis † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Upper respiratory tract infection † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     1  
Urinary tract infection † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Injury, poisoning and procedural complications      
Chemical poisoning † 1    
# participants affected / at risk     1/758 (0.13%)     1/761 (0.13%)  
# events     1     1  
Femur fracture † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Head injury † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Thermal burn † 1    
# participants affected / at risk     1/758 (0.13%)     2/761 (0.26%)  
# events     1     2  
Traumatic shock † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     1/758 (0.13%)     1/761 (0.13%)  
# events     1     1  
Haemoglobin decreased † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Hepatic enzyme increased † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Neutrophil count decreased † 1    
# participants affected / at risk     1/758 (0.13%)     2/761 (0.26%)  
# events     1     2  
Metabolism and nutrition disorders      
Electrolyte imbalance † 1    
# participants affected / at risk     0/758 (0.00%)     1/761 (0.13%)  
# events     0     2  
Kwashiorkor † 1    
# participants affected / at risk     5/758 (0.66%)     9/761 (1.18%)  
# events     5     9  
Malnutrition † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Marasmus † 1    
# participants affected / at risk     3/758 (0.40%)     4/761 (0.53%)  
# events     3     5  
Nervous system disorders      
Febrile convulsion † 1    
# participants affected / at risk     5/758 (0.66%)     0/761 (0.00%)  
# events     5     0  
Hydrocephalus † 1    
# participants affected / at risk     1/758 (0.13%)     0/761 (0.00%)  
# events     1     0  
Respiratory, thoracic and mediastinal disorders      
Aspiration † 1    
# participants affected / at risk     1/758 (0.13%)     2/761 (0.26%)  
# events     1     2  
Pneumonia aspiration † 1    
# participants affected / at risk     2/758 (0.26%)     0/761 (0.00%)  
# events     2     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (14.1)




  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.


  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:


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00074412     History of Changes
Other Study ID Numbers: HPTN 046, 10142
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