Tenofovir As Prevention Of Hepatitis b Mother-to-child Transmission (TA-PROHM)

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.

Study Overview

• Status: Unknown
• Conditions: Pregnancy; Hepatitis B Chronic Infection
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate; Device: Rapid tests HBe Ag

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.

• Study Type: Interventional
• Enrollment (Anticipated): 933
• Phase: Phase 4

Contacts and Locations

Study Locations

• Cambodia
  • Kampong Cham, Cambodia
    • Kampong Cham Provincial Hospital
  • Phnom Penh, Cambodia
    • Calmette Hospital
  • Phnom Penh, Cambodia
    • National Mother and Child Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBs Ag positive; tenofovir 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	Drug: Tenofovir disoproxil fumarate; tenofovir disoproxil fumarate 300 mg one tablet once daily from 24 weeks of amennorrhea to 6 weeks post-partum for HBe Ag positive women only.; Other Names: TDF; Device: Rapid tests HBe Ag; For all HBs Ag positive women

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of active HBV infection in new-born at 6 months of life	The proportion will be estimated by HBs Ag positivity	6 months post-partum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Process and acceptability of the screening phase	Proportion of women with screening proposed among those eligible in antenatal consultation (ANC)	Enrollement
Process and acceptability of the screening phase	Proportion of women with a done screening among those to whom screening was proposed	Enrollement
Process and acceptability of the screening phase	Proportion of women with a given results in less than one day among those to whom the test was made	Enrollement
Process and acceptability of the screening phase	Care-giver satisfaction regarding the strategy (estimated by questionnaires)	Enrollement

Other Outcome Measures

Outcome Measure	Time Frame
Process and acceptability of the drug's intervention	Enrollement
Proportion of women with viral load > 6 Log among those HBe Ag negative	Enrollement
Proportion of new-born with positive HBs Ag at 6 months according to treatment duration, initial and delivery viral load level	6 months post-partum
Decrease curve of HBV VL after TDF initiation over time	From enrollement to 8 weeks or 6 months post-partum
Occurrence of maternal adverse events including serious adverse events and adverse events grade 3 or 4	From enrollement to 6 months post-partum
Proportion of women needing treatment continuation in post-partum among those to whom treatment was initiated	6 weeks post-partum
Occurrence of acute exacerbation after treatment interruption	From 8 weeks post-partum to 6 months post-partum

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Samsorphea CHHUN, MD, Calmette Hospital

Publications and helpful links

General Publications

• Segeral O, Dim B, Durier C, Nhoueng S, Chhim K, Sovann S, Yom S, Vong C, Yin S, Ros B, Ky V, Pech S, Nem B, Hout K, Guillebaud J, Ear E, Caroupaye-Caroupin L, Rekacewicz C, Fernandez L, Laurent D, Yay C, Kim R, Meyer L, Chhun S; Laurence Borand for the ANRS-MIE TA PROHM Study Group. Immunoglobulin-free strategy to prevent HBV mother-to-child transmission in Cambodia (TA-PROHM): a single-arm, multicentre, phase 4 trial. Lancet Infect Dis. 2022 Aug;22(8):1181-1190. doi: 10.1016/S1473-3099(22)00206-7. Epub 2022 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): March 31, 2020

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 17, 2016
• First Posted (Estimate): October 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 16, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: ANRS 12345

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No