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Tenofovir As Prevention Of Hepatitis b Mother-to-child Transmission

Phase 4
Conditions
Hepatitis B Chronic Infection
Pregnancy
Interventions
Device: Rapid tests HBe Ag
Registration Number
NCT02937779
Lead Sponsor
ANRS, Emerging Infectious Diseases
Brief Summary

The World Health Organization recommends that all high endemic countries for HBV infection based their mother to child transmission prevention strategies on vaccination of all children and administration of immunoglobulins (HBIG) to infants born to infected mothers in the first 24 hours after birth. Lack of access to antenatal screening and to HBIG significantly results in failure of this strategy in many countries. Moreover, despite sero-vaccination, 10 to 15% of infants of mothers that are positive for HBsAg and HBeAg are still infected, as high levels of HBV replication occurring in the third quarter of pregnancy act as a major risk factor.

The objective of this study is to assess the effectiveness of an operational strategy to prevent HBV mother-to-child transmission (MTCT) in Cambodia based on the use of rapid tests HBs Ag and HBe Ag to screen HBV infection and a treatment by TDF for patients with a positive HBeAg test with a "test and treat" strategy for those seen for Antenatal Care (ANC) from 24 weeks of amenorrhea. In all cases, vaccination of the newborn will be carried out according to the national protocol in Cambodia i.e. 4 injections at 24 hours, 6, 10 and 14 weeks of age.

A phase IV multicenter observational and interventional non randomized prospective study will be conducted in 4 maternity in Cambodia.

The primary outcome will be the proportion of active HBV infection in new-born at 6 months of life estimated by HBs Ag positivity.

The study will aim to document the acceptability and the operational implementation of the study using rapid tests usable in all health centers and a drug available in all the country thanks to HIV national program. The results will be helpful for Cambodian government in order to implement guidelines and algorithm follow-up for HBV-infected pregnant women.

Detailed Description

Principal objective: Assess the effectiveness of a strategy to prevent HBV mother-to-child transmission (MTCT) in Cambodia based on the use of rapid tests HBs Ag and HBe Ag to screen HBV infection and a treatment by TDF for patients with a positive HBeAg test with a "test and treat" strategy for those seen for Antenatal Care (ANC) from 24 weeks of amenorrhea.

Secondary objectives Assess the feasibility and acceptability for patients and health care providers of the rapid tests screening strategy Assess the acceptability of the test and treat strategy for patients seen after 24 weeks of amenorrhea Describe the HBV viral load (VL) decrease caused by the TDF Estimate the rate of HBV transmission to newborns according to the time spent on TDF as well as initial viral load level and delivery viral load level Estimate the rate of HBV transmission to newborns for HBe Ag negative women Describe the correlation between HBV viral load level and HBe Ag status Describe subgroups of mothers and new-borns for which the strategy seems more effective Assess TDF safety in mothers Analyse the cost-effectiveness of the strategy compare to international guidelines (WHO, APASL)

Each woman will be informed of the objectives and the total duration of the study as well as the benefits and risks to participate. An information sheet in Khmer will be given to each woman. The study will be composed of two phases of information's and consent. The first one will be done during the HBs Ag screening using rapid test; the screening will be proposed to all pregnant women attending ANC in one of the affiliated centres. The second phase will be done during the inclusion visit and will concern only HBs Ag positive women. The study will concern only HBs Ag positive women with 1) follow up of all HBsAg positive women from inclusion up to 6 months postpartum 2) For HBeAg positive women, initiation of treatment by fumarate de tenofovir disoproxil (Viread®), with a daily administration of one 300mg pill. Women will be treated from 24 weeks of amenorrhea until 6 weeks post-partum. For women with first ANC after 24 weeks of amenorrhea, treatment will begin the day of inclusion. Treatment will be given for 4 weeks and adherence will be estimated. In all cases, vaccination of the newborn will be carried out according to the national protocol in Cambodia i.e. 4 injections at 24 hours, 6, 10 and 14 weeks of age.

A total of 933 positive HBs Ag pregnant women will be enrolled including 280 HBe Ag positive women and 653 HBe negative women.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
933
Inclusion Criteria
  • >= 18 years old the day of inclusion
  • Pregnancy
  • Positive HBs Ag
  • Informed consent obtained with information sheet given and explained and the consent form signed by the participant of the project investigator at the latest the day of the inclusion
Exclusion Criteria
  • Women refusing HBs Ag test
  • HIV co-infection
  • HCV co-infection
  • HBV treatment ongoing at the day of inclusion
  • Creatinine clearance < 30 mL/min
  • Severe gravidic disease present at inclusion involving life threatening to the mother and/or the child
  • Evidence of pre-existing fetal anomalies incompatible with the child's life
  • Imminent child's birth defined as cervix dilatation up to 7 centimeters
  • Intention to deliver in a maternity not linked to the study
  • Any concomitant medical condition that, according to the clinical site investigator would contraindicate participation in the study.
  • Concurrent participation in any other clinical trial without written agreement of the two study teams

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HBs Ag positiveRapid tests HBe Agtenofovir disoproxil fumarate 300 mg one tablet once daily from 24 weeks of amennorrhea to 6 weeks post-partum for positive Hbe Ag women. No treatment for negative HBe Ag women
HBs Ag positiveTenofovir disoproxil fumaratetenofovir disoproxil fumarate 300 mg one tablet once daily from 24 weeks of amennorrhea to 6 weeks post-partum for positive Hbe Ag women. No treatment for negative HBe Ag women
Primary Outcome Measures
NameTimeMethod
Proportion of active HBV infection in new-born at 6 months of life6 months post-partum

The proportion will be estimated by HBs Ag positivity

Secondary Outcome Measures
NameTimeMethod
Process and acceptability of the screening phaseEnrollement

Care-giver satisfaction regarding the strategy (estimated by questionnaires)

Trial Locations

Locations (3)

Kampong Cham Provincial Hospital

🇰🇭

Kampong Cham, Cambodia

Calmette Hospital

🇰🇭

Phnom Penh, Cambodia

National Mother and Child Health Center

🇰🇭

Phnom Penh, Cambodia

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