Efficacy and Safety of Infant Peri-Exposure Prophylaxis With Lamivudine to Prevent HIV-1 Transmission by Breastfeeding - Tabular View

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Tracking Information

First Received Date ^†

January 15, 2008

Last Updated Date

October 13, 2008

Start Date ^†

January 2009

Current Primary Outcome Measures ^†

Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) [ Time Frame: between day 7 and 38 weeks of age ] [ Designated as safety issue: No ]

Original Primary Outcome Measures ^†

Same as current

Change History

Complete list of historical versions of study NCT00640263 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^†

HIV-1 free survival [ Time Frame: at 38 weeks of age ] [ Designated as safety issue: No ]
HIV-1 free survival [ Time Frame: at one year of age ] [ Designated as safety issue: No ]
safety of long-term prophylaxis with lamivudine [ Time Frame: until 38 weeks of age ] [ Designated as safety issue: Yes ]
safety of long-term prophylaxis with lamivudine [ Time Frame: until one year of age ] [ Designated as safety issue: Yes ]

Original Secondary Outcome Measures ^†

Same as current

Descriptive Information

Brief Title ^†

Efficacy and Safety of Infant Peri-Exposure Prophylaxis With Lamivudine to Prevent HIV-1 Transmission by Breastfeeding

Official Title ^†

Double Blind Randomised Placebo-Controlled Trial of the Efficacy and Safety of Infant Peri-Exposure Prophylaxis With Lamivudine to Prevent HIV-1 Transmission by Breastfeeding

Brief Summary

The PROMISE PEP study is a clinical trial that will measure the efficacy and the safety of prolonged peri-exposure prophylaxis (PEP) with lamivudine (3TC) 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 placebo-controlled clinical trial.

Intervention:

Infants will be randomised to receive 3TC or placebo once 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 measure the efficacy of PEP with 3TC once daily from day 7 until 4 weeks after cessation of BF (maximum duration of prophylaxis: 38 weeks for a maximum duration of breastfeeding of 34 weeks) on the risk of postnatal HIV-1 acquisition between 7 days and 38 weeks of age

Secondary objectives:

To measure the efficacy of PEP on HIV-1 free survival at 38 weeks and at one year of age ;
To assess the safety of long-term prophylaxis with 3TC (including adverse events, resistance to lamivudine and growth) until 38 weeks and at one year of age ;
To build clinical trials capacity at the four study sites ;

Main endpoint:

Acquisition of HIV-1 (as determined by HIV-1 DNA PCR) between day 7 and 38 weeks of age.

Study population:

Seronegative 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 a standard 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 one year and the total study duration is five years.

Expected outcome:

This study will measure the efficacy of a new drug regimen to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies for 34 weeks. If found to be sufficiently efficacious, the regimen would contribute to counteract the existing contradiction between optimal infant feeding and MTCT through breast milk.

Detailed Description

Study Phase

Phase III

Study Type ^†

Interventional

Study Design ^†

Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Condition ^†

HIV Infections

Intervention ^†

Drug: lamivudine (3TC)
Drug: Placebo

Study Arms / Comparison Groups

Experimental: infant peri-exposure prophylaxis with lamivudine
Placebo Comparator: Placebo

Publications *

Kourtis AP, Jamieson DJ, de Vincenzi I, Taylor A, Thigpen MC, Dao H, Farley T, Fowler MG. Prevention of human immunodeficiency virus-1 transmission to the infant through breastfeeding: new developments. Am J Obstet Gynecol. 2007 Sep;197(3 Suppl):S113-22. Review.

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^†

Not yet recruiting

Enrollment ^†

1500

Estimated Completion Date

December 2012

Estimated Primary Completion Date

December 2011 (final data collection date for primary outcome measure)

Eligibility Criteria ^†

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 ≥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

Gender

Both

Ages

up to 9 Days

Accepts Healthy Volunteers

Contacts ^††

Contact: Philippe Vande Perre, MD, PhD	+33 467336886	p-van_de_perre@chu-montpellier.fr
Contact: Thorkild Tylleskär, MD, PhD	+47 55974975	Thorkild.Tylleskar@cih.uib.no

Location Countries ^†

Burkina Faso, South Africa, Uganda, Zambia

Expanded Access Status

Administrative Information

NCT ID ^†

NCT00640263

Responsible Party

Claire Rekacewicz, French National Agency for Research on AIDS and Viral Hepatitis

Secondary IDs ^††

EDCTP : RCN 183600

Study Sponsor ^†

French National Agency for Research on AIDS and Viral Hepatitis

Collaborators ^††

Europe Developing Countries Clinical Trials Partnership (EDCTP)
The Research Council of Norway
Swedish International Development Cooperation Agency
Université Montpellier
University of Bergen

Investigators ^†

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:	Cheryl Nikodem, DCurMCurBCur	University of the Western Cape, South Africa
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)

Information Provided By

French National Agency for Research on AIDS and Viral Hepatitis

Verification Date

October 2008

^† Required WHO trial registration data element.
^†† WHO trial registration data element that is required only if it exists.