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Prevention of Mother-to-child Transmission of HIV-1 Using a Responsive Intervention (PROMISE-EPI)

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: NCT03870438
Recruitment Status : Active, not recruiting
First Posted : March 12, 2019
Last Update Posted : November 30, 2021
Sponsor:
Collaborators:
University Teaching Hospital, Lusaka, Zambia
Centre Muraz
Institut National de la Santé Et de la Recherche Médicale, France
University of Bergen
Information provided by (Responsible Party):
ANRS, Emerging Infectious Diseases

Brief Summary:
The second visit of the Expanded Programme of Immunization when the child is 2 months old (EPI-2) represents a unique opportunity to link the EPI and PMTCT programmes and to introduce preventive and therapeutic rescue interventions in order to: 1) Assess the efficacy of the PMTCT cascade up to 2 months postpartum; 2) Allow at least 80% of HIV-1-infected infants identified at the second EPI visit who were not involved in HIV care to initiate ARVs at the earliest, but no later than 2 months after confirmation of HIV diagnosis; 3) Reduce HIV-1 transmission to less than 3% between 2 and 12 months among exposed children who completed the second EPI visit

Condition or disease Intervention/treatment Phase
HIV-1 Drug: Lamivudine Oral Solution Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1506 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase III, Randomized Control Trial, parallel, open-label, multi-country and multi-centre trial
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Prevention of Mother-to-child Transmission of HIV-1: Programme Evaluation and Innovative Responsive Intervention Integrated in the Expanded Programme of Immunization. PROMISE-EPI Study
Actual Study Start Date : December 14, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Vaccines
Drug Information available for: Lamivudine

Arm Intervention/treatment
Experimental: Intervention

Children infected with HIV-1 will be referred to the National Programme for confirmed HIV diagnosis and immediate ART.

For children that are not HIV-1 infected, the results on the mother's viral load will guide the next steps:

Mothers with a detectable plasma viral load (≥ 1000 copies/mL): their children will be initiated on lamivudine oral solution.

Mothers with an undetectable viral loads (<1000 copies/mL): their children will not be initiated on lamivudine oral solution at 6-8 weeks of age. However, additional monitoring on the viral load of the mother and the diagnosis of the child will take place at 6 months: If the maternal plasmatic viral load is ≥ 1000 copies/mL, the child will be initiated on lamivudine oral solution.

Drug: Lamivudine Oral Solution
In the intervention arm, HIV-1 negative children with HIV-1 positive mothers who have an HIV-1 viral load ≥ 1000 copies/ml will receive lamivudine syrup orally (7.5 mg twice daily if 2 to 4 kg; 25 mg twice a day if weight <8 kg; and 50 mg twice a day if weight >8 kg). The intervention will last a maximum of 10 months (until the baby is 12 months old or until the confirmed end of breastfeeding). Breastfeeding will be considered to be ceased if the mother confirms she is no longer breastfeeding for 2 consecutive monthly visits

No Intervention: Control
Routine Option B+ national guidelines including HIV-1 plasmatic viral load testing will be adhered to. Visits will take place at 6-8 weeks, 6 and 12 months post-partum to collect samples from the mother for the analysis of viral load results at 12 months. In addition, at 6-8 weeks, 6 and 12 months post-partum, POC tests will be done for the diagnosis of HIV-1 in their infants (by HIV-1 DNA PCR) and results will be shared within 2 hours. Children infected with HIV-1 will be referred to the National Programme for confirmed diagnosis and immediate ART.



Primary Outcome Measures :
  1. Prevention of HIV-1 transmission from HIV-1-positive mothers to their breastfeeding children [ Time Frame: 12 months ]
    Postnatal HIV-1 transmission rates at 12 months in infants exposed to HIV-1 through breastfeeding


Secondary Outcome Measures :
  1. Assessment of PMTCT cascade [ Time Frame: 2 months ]

    Proportion of women attending the 6-8 week EPI visit who, per the records in the antenatal care clinics:

    • had attended ANC/PMTCT clinic at least once during their pregnancy
    • had been tested for HIV-1 antenatally or during childbirth
    • are HIV-1 infected Proportion of children who were HIV-1 tested with PCR at birth (Zambia only) (per the records in the antenatal care or birth clinics)

    Proportion of women with a positive HIV test who had:

    • initiated ART during pregnancy or following childbirth (per the records in the antenatal care clinics)
    • undetectable plasma viral load (<1000 HIV RNA copies/mL) as per the results obtained with the Point of Care HIV-1 PCR Viral Load in the study Proportion of babies with a positive HIV-1 PCR (as per the results obtained with the Point of Care HIV-1 PCR Qualitative in the study)

  2. Access to ART for HIV-1 positive children [ Time Frame: 6 months ]
    Proportion of HIV-infected infants identified during the second EPI visit and who were not engaged in HIV care at this time, but who will be initiated on ART within 2 months after this visit, or if infected during follow-up- within 2 months after diagnosis, (as per the results obtained with the Point of Care HIV-1 PCR Qualitative in the study)

  3. Evaluation of the diagnostic performance of plasma HIV viral load in comparison to breastmilk viral load to identify infants at risk of transmission at 6-8 weeks, 6 months and 12 months [ Time Frame: 6-8 weeks, 6 months, 12 months ]
    Proportion of plasma HIV-1 viral load levels concordant with breast milk HIV-1 viral load levels

  4. Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation: [ Time Frame: 12 months ]
    To assess the non-inferiority of a single-drug versus triple-drug prophylactic regimen to prevent HIV transmission at one year of age (HIV-transmission rate from EPI-2 visit to 12 months of age)

  5. Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation: [ Time Frame: 12 months ]
    To assess the non-inferiority of a single-drug versus triple-drug prophylactic regimen in terms of HIV-1 free survival at one year of age.

  6. Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population following the 2020 Zambian guidelines implementation [ Time Frame: 12 months ]
    Adverse events rates at 12 months, including death and Grade 3 or 4 events on the paediatric DAIDS scale

  7. Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm) [ Time Frame: 12 months ]
    To assess the efficacy of a responsive intervention package to prevent HIV transmission at one year of age (HIV-transmission rate from EPI-2 visit to 12 months of age)

  8. Evaluation of the efficacy for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm) [ Time Frame: 12 months ]
    To assess the efficacy of a responsive intervention package to improve HIV-1 free survival at one year of age

  9. Evaluation of the safety for all the participants of the intervention arm and the comparison arm sub-population before the introduction of the 2020 Zambian guidelines (including Burkina Faso control arm) [ Time Frame: 12 months ]
    Adverse events rates at 12 months, including death and Grade 3 or 4 events on the paediatric DAIDS scale



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   HIV-1-positive breastfeeding mothers of HIV-1-negative children (female or male)
Accepts Healthy Volunteers:   No
Criteria

For HIV+ women who give consent, the measurement of their HIV-1 viral load and the detection of HIV-1 DNA in their children will be assessed.

Inclusion Criteria:

A mother/infant pair will be included in the Phase III trial if the infant:

  • Is a singleton
  • Is breastfed at 2 months and the mother intends to continue breastfeeding for at least 4 months (until her child is 6 months old)
  • Has a negative HIV-1 PCR POC test at 2 months of age
  • Has a mother who:
  • Is the accompanying person to visit 2 of the EPI
  • Is 15 years of age or older (in Zambia) and 20 years of age or older (in Burkina Faso) or
  • If between 15 and 19 years of age (inclusive) in Burkina Faso, and is accompanied by a referent adult of her choice representing her interests and the interests of the child (parent, family member or guardian, member of an association, etc.)
  • Has been confirmed to be infected with HIV-1 (with or without HIV-2)
  • Has signed the consent form to participate For the mother in Zambia, the consent must be signed by herself and a witness; For the mother in Burkina Faso, the consent must be signed by herself and a witness (if illiterate) and/or a referent adult (if under 20 years of age in Burkina Faso).

For the child in Zambia, the consent must be signed by the mother. For the child in Burkina Faso, the consent must be signed by the mother and/or a referent adult (if under 20 years of age in Burkina Faso. In Burkina Faso, both parents need to sign the consent unless the mother exercises sole parental authority or if obtaining the father's consent is likely to endanger the mother and her child. In Zambia, the mother exercises sole parental authority.

Exclusion Criteria:

A mother-child couple will not be included if the child:

  • Has clinical symptoms or biological abnormalities of DAIDS classification 3 or 4 for adverse events on the day of inclusion
  • Has a severe congenital malformation
  • Has a known allergy to the study drug or its components
  • Takes emtricitabine concomitantly
  • Has a mother who:
  • Lives outside the study area or intending to move from the area within the next 12 months
  • Is participating in another clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03870438


Locations
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Burkina Faso
CSPS and CMA of Do and Dafra districts
Bobo-Dioulasso, Burkina Faso
CSPS and CMA of Baskuy and Boulmiougou districts
Ouagadougou, Burkina Faso
Zambia
Bauleni
Lusaka, Zambia
Chaisa
Lusaka, Zambia
Chilenje Level 1 hospital
Lusaka, Zambia
Matero Main
Lusaka, Zambia
Sponsors and Collaborators
ANRS, Emerging Infectious Diseases
University Teaching Hospital, Lusaka, Zambia
Centre Muraz
Institut National de la Santé Et de la Recherche Médicale, France
University of Bergen
Investigators
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Principal Investigator: Philippe Van de Perre, MD, PhD Institut National de la Santé Et de la Recherche Médicale, France
Publications:
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Responsible Party: ANRS, Emerging Infectious Diseases
ClinicalTrials.gov Identifier: NCT03870438    
Other Study ID Numbers: ANRS 12397 PROMISE-EPI
First Posted: March 12, 2019    Key Record Dates
Last Update Posted: November 30, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ANRS, Emerging Infectious Diseases:
HIV-1
PMTCT
Point of Care
PrEP
Zambia
Burkina Faso
Expanded Program of Immunization (EPI)
Additional relevant MeSH terms:
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Lamivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents