Trial of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV Transmission

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00099359
First received: December 10, 2004
Last updated: October 26, 2012
Last verified: February 2011
Results First Received: April 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: Disease Transmission, Vertical
Vertical Human Immunodeficiency Virus Transmission
HIV Infections
Interventions: Drug: Zidovudine
Drug: Nevirapine (NVP)
Drug: Epivir (3TC)
Drug: Nelfinavir (NFV)

  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
The first subject was enrolled on 02/27/2004 and the study ended 02/28/2011. A total of 17 sites in Brazil, South Africa, Argentina and the U.S. participated in the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A (ZDV Only) Standard of care ( Zidovudine only). 12 mg PO BID if BW>2000 grams ; 8 mg PO BID if BW</= 2000 grams
ARM B (ZDV + NVP)

Standard of care (Zidovudine) plus Nevirapine (NVP)

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams

ARM C (ZDV + 3TC + NFV)

Standard of Care (Zidovudine) plus 2 weeks of Epivir (3TC) and Nelfinavir (NFV) 3TC, given for 2 weeks: 6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 – 3000 grams 100 mg PO BID if BW < 2000 grams


Participant Flow:   Overall Study
    Arm A (ZDV Only)     ARM B (ZDV + NVP)     ARM C (ZDV + 3TC + NFV)  
STARTED     581     580     574  
COMPLETED     527     515     506  
NOT COMPLETED     54     65     68  
Death                 11                 15                 17  
Withdrawal by Subject                 19                 19                 23  
Lost to Follow-up                 15                 24                 24  
moved out of area                 9                 7                 4  



  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
Arm A (ZDV Only) Standard of care ( Zidovudine only). 12 mg PO BID if BW>2000 grams ; 8 mg PO BID if BW</= 2000 grams
ARM B (ZDV + NVP)

Standard of care (Zidovudine) plus Nevirapine (NVP)

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams

ARM C (ZDV + 3TC + NFV)

Standard of Care (Zidovudine) plus 2 weeks of Epivir (3TC) and Nelfinavir (NFV) 3TC, given for 2 weeks: 6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 – 3000 grams 100 mg PO BID if BW < 2000 grams

Total Total of all reporting groups

Baseline Measures
    Arm A (ZDV Only)     ARM B (ZDV + NVP)     ARM C (ZDV + 3TC + NFV)     Total  
Number of Participants  
[units: participants]
  581     580     574     1735  
Age  
[units: weeks]
Mean ± Standard Deviation
       
Gestational Age in Weeks     39  ± 1.7     39  ± 1.5     39  ± 1.7     39  ± 1.7  
Gender  
[units: participants]
       
Female     298     303     281     882  
Male     283     277     293     853  
Region of Enrollment  
[units: participants]
       
United States     4     4     4     12  
Puerto Rico     0     1     1     2  
Argentina     10     6     11     27  
Brazil     409     408     402     1219  
South Africa     158     161     156     475  



  Outcome Measures
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1.  Primary:   Infant HIV Infection Status   [ Time Frame: 3 months ]
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Measure Type Primary
Measure Title Infant HIV Infection Status
Measure Description Intrapartum HIV infection at 3 Months
Time Frame 3 months  
Safety Issue No  

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.
All infants with HIV-1 test results except infants infected at birth (i.e. in utero infections) were included in these analysis.

Reporting Groups
  Description
ARM A (ZDV - Standard of Care)

ZDV (standard of care), given for 6 weeks:

12 mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams

ARM B (ZDV + NVP) plus NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose : 12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams
ARM C (ZDV +3TC+NFV)

ZDV (standard of care) plus 3TC, given for 2 weeks:

6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 - 3000 grams 100 mg PO BID if BW < 2000 grams


Measured Values
    ARM A (ZDV - Standard of Care)     ARM B (ZDV + NVP)     ARM C (ZDV +3TC+NFV)  
Number of Participants Analyzed  
[units: participants]
  566     562     556  
Infant HIV Infection Status  
[units: participants]
  24     11     12  


Statistical Analysis 1 for Infant HIV Infection Status
Groups [1] All groups
Method [2] multiple comparison
P Value [3] .046
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Hochberg’s modified Bonferroni method was used to adjust the significance level for comparisons between arms.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Overall comparison of 3 KM curves using an extension of the M-H test was performed. Results indicated a significant difference therefore a 2nd stage analysis was done to compare each pair of transmission rates, using 2-sample Mantel-Haenzel tests.



2.  Primary:   Participants With Serious Adverse Events   [ Time Frame: through age 6 months. ]

3.  Secondary:   Infant HIV-1 Infection Status   [ Time Frame: birth ]

4.  Secondary:   Participant Deaths   [ Time Frame: through age 6 months ]

5.  Secondary:   3TC and NFV Pharmacokinetics   [ Time Frame: through age 14 days ]

6.  Secondary:   Risk Factors for Perinatal HIV-1 Transmission   [ Time Frame: through age 3 months ]

7.  Secondary:   NVP Pharmacokinetics   [ Time Frame: 14 days ]

8.  Secondary:   Clinical Covariates of HIV-1 Infection   [ Time Frame: through age 3 months ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Margaret Camarca, Project Director
Organization: Westat
phone: 301-517-4128
e-mail: margaretcamarca@westat.com


Publications of Results:

Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00099359     History of Changes
Other Study ID Numbers: NICHD/HPTN 040 (P1043)
Study First Received: December 10, 2004
Results First Received: April 25, 2012
Last Updated: October 26, 2012
Health Authority: United States: Food and Drug Administration