Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00640263
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : April 14, 2014
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
The Research Council of Norway
Swedish International Development Cooperation Agency (SIDA)
Université Montpellier
University of Bergen
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )

Tracking Information
First Submitted Date  ICMJE January 15, 2008
First Posted Date  ICMJE March 21, 2008
Last Update Posted Date April 14, 2014
Study Start Date  ICMJE December 2009
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) [ Time Frame: between day 7 and 50 weeks of age ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) [ Time Frame: between day 7 and 38 weeks of age ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2009)
  • HIV-1 free survival [ Time Frame: at 50 weeks of age ]
  • HIV-1 free survival [ Time Frame: at one year of age ]
  • safety of long-term prophylaxis [ Time Frame: until 50 weeks of age ]
  • safety of long-term prophylaxis [ Time Frame: until one year of age ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
  • HIV-1 free survival [ Time Frame: at 38 weeks of age ]
  • HIV-1 free survival [ Time Frame: at one year of age ]
  • safety of long-term prophylaxis with lamivudine [ Time Frame: until 38 weeks of age ]
  • safety of long-term prophylaxis with lamivudine [ Time Frame: until one year of age ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Efficacy and Safety of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
Official Title  ICMJE A Randomised Controlled Trial Comparing the Efficacy of Infant Peri-exposure Prophylaxis With Lopinavir/Ritonavir (LPV/r) Versus Lamivudine to Prevent HIV-1 Transmission by Breastfeeding
Brief Summary

The ANRS 12174 study is a clinical trial that will compare the efficacy and safety of prolonged infant peri-exposure prophylaxis (PEP) with Lopinavir/Ritonavir (LPV/r) versus Lamivudine to prevent HIV-1 transmission through breast milk in children born to HIV-1-infected mothers not eligible for HAART and having benefited from perinatal antiretroviral (ART) regimens. The study will recruit 1500 mother-infant pairs in 4 African countries.

Study design:

PROMISE PEP is a multinational, randomised double-blind controlled clinical trial.

Intervention:

Infants will be randomised to receive LPV/r or 3TC twice daily from day seven (± 2 days) after birth until 4 weeks after cessation of breastfeeding (BF). We will recommend exclusive BF (EBF) up till including the 26th week of life followed by a relatively rapid (maximum of 8 weeks) cessation period. The maximum duration of PEP will thereby be 38 weeks.

Primary objective:

To compare the efficacy of infant LPV/r (40/10mg twice daily if 2-4kg and 80/20mg twice daily if >4kg) vs. Lamivudine 7,5mg twice daily if 2-4kg, 25mg twice daily if 4-8kg and 50mg twice daily if >8kg) from day 7 until 4 weeks after cessation of BF (maximum duration of prophylaxis: 50 weeks for a maximum duration of breastfeeding of 46 weeks) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age.

Secondary objectives:

  • To assess the safety of long-term infant prophylaxis with LPV/r versus Lamivudine (including resistance, adverse events and growth) until 50 weeks.
  • HIV-1-free survival until 50 weeks
  • To build clinical trials capacity at the four study sites.

Main endpoint:

Acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age

Study population:

HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants and who have benefited from the national prevention of mother to child transmission (PMTCT) program during pregnancy and delivery. The study will recruit 1500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia.

Study duration:

Infants will be followed up for 50 weeks and the total study duration is five years.

Expected outcome:

This study will inform on the relative advantages (efficacy) and drawbacks of two interventions to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies. If found to be safe and efficacious, the regimens would avoid the existing contradiction between optimal infant feeding and the prevention of MTCT through breast milk. Clinical trial capacity development will improve the future quality of trials conducted in these countries.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: lopinavir/ritonavir (LPV/r)
    Oral liquid formulation lopinavir/ritonavir(80 mg lopinavir + 20 mg ritonavir/mL); Dosing : 40/10mg twice daily if infant weight is between 2 to 4 kg and 80/20mg twice daily if infant weight is above 4kg The lopinavir/ritonavir will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.
  • Drug: Lamivudine (3TC)

    Oral liquid solution lamivudine(10 mg/mL). Dosing : 7,5 mg twice daily if if infant weight is between 2 to 4 kg ; 25 mg twice daily if infant weight is between 4 to 8 kg ; 50 mg twice daily if infant weight is above 8kg.

    The lamivudine will be given to the baby from Day 7 postnatal until 4 weeks after the cessation of breastfeeding. During the treatment period, dosing will be adapted according to the infant weight.

Study Arms  ICMJE
  • Experimental: 1
    infant peri-exposure prophylaxis with lopinavir/ritonavir
    Intervention: Drug: lopinavir/ritonavir (LPV/r)
  • Active Comparator: 2
    infant peri-exposure prophylaxis with lamivudine
    Intervention: Drug: Lamivudine (3TC)
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
Estimated Enrollment  ICMJE
 (submitted: March 20, 2008)
1500
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: A baby will be included if she/he:

  • is a singleton
  • is breastfed at day 7 by her/his mother and her/his mother intends to continue breastfeeding for at least 6 months
  • has a post-partum blood sample with a negative HIV-1 DNA PCR test result at day 7 (+/- 2 days)
  • has received ART as part of PMTCT

and if the mother:

  • has reached the local legal age for participating in medical research studies
  • is shown to be HIV-1 infected (with or without HIV-2 infection) and is not eligible for HAART or is not taking HAART
  • has received a perinatal antiretroviral prophylaxis during pregnancy and delivery,
  • has a CD4 count above the threshold of HAART initiation in pregnant women according to the national recommendation in each site (minimum 230 cells/µL),
  • resides within the study area and is not intending to move out of the area in the next year
  • gives assent for the infant to participate and gives consent to participate

Exclusion Criteria:

  • S/he presents clinical symptoms and/or biological abnormalities equal to or greater than grade II of the ANRS classification for adverse event on the day of enrolment
  • S/he presents with serious congenital malformation(s)
  • Her/his birth weight is lower than 2.0 kg
  • Her/his antiretroviral prophylaxis is extending beyond day 7
  • The mother has participated in the trial for a previous pregnancy
  • S/he and her/his mother are participating in another clinical trial on the day of enrolment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 9 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Burkina Faso,   South Africa,   Uganda,   Zambia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00640263
Other Study ID Numbers  ICMJE ANRS 12174 PROMISE-PEP
EDCTP : RCN 183600
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
Study Sponsor  ICMJE French National Agency for Research on AIDS and Viral Hepatitis
Collaborators  ICMJE
  • European and Developing Countries Clinical Trials Partnership (EDCTP)
  • The Research Council of Norway
  • Swedish International Development Cooperation Agency (SIDA)
  • Université Montpellier
  • University of Bergen
Investigators  ICMJE
Study Chair: Philippe Vande Perre, MD, PhD University of Montpellier, France
Study Chair: Thorkild Tylleskär, MD, PhD Centre For International Health
Principal Investigator: Nicolas Meda, MD, PhD University of Ouagadougou, Burkina Faso
Principal Investigator: James K Tumwine, MD, PhD Dept of Paediatrics and Child Health, Makerere University, Uganda
Principal Investigator: Chipepo Kankasa, MD Dept of Paediatrics and Child Health, School of Medicine, University of Zambia
Principal Investigator: Justus Hofmeyer, MD East London Hospital Complex
Principal Investigator: Eva-Charlotte Ekström, PhD Uppsala University, Uppsala, Sweden
Principal Investigator: Stephane Blanche, MD, PhD Hôpital Necker Enfants Malades, Université Paris V (EA 3620)
PRS Account French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Verification Date April 2014

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