## Protocol Section
### Identification Module
**NCT ID:** NCT02937779

**Acronym:** TA-PROHM

**Brief Title:** Tenofovir As Prevention Of Hepatitis b Mother-to-child Transmission

**Official Title:** Tenofovir As Prevention Of Hepatitis b Mother-to-child Transmission

#### Organization Study ID Info
**ID:** ANRS 12345
#### Organization
**Class:** OTHER_GOV
**Full Name:** ANRS, Emerging Infectious Diseases
### Status Module
#### Completion Date
**Date:** 2020-03-31

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** ACTIVE_NOT_RECRUITING
#### Last Update Post Date
**Date:** 2019-10-16

**Type:** ACTUAL

**Last Update Submit Date:** 2019-10-15

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2020-03-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2017-10-04

**Type:** ACTUAL

**Status Verified Date:** 2019-10

#### Study First Post Date
**Date:** 2016-10-19
**Type:** ESTIMATED
**Study First Submit Date:** 2016-10-17
**Study First Submit QC Date:** 2016-10-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER_GOV

**Name:** ANRS, Emerging Infectious Diseases

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Hepatitis B Chronic Infection

- Pregnancy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 933

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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

**Intervention Names:**

- Drug: Tenofovir disoproxil fumarate

- Device: Rapid tests HBe Ag

**Label:** HBs Ag positive

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- HBs Ag positive

**Description:** 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.

**Name:** Tenofovir disoproxil fumarate

**Other Names:**

- TDF

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- HBs Ag positive

**Description:** For all HBs Ag positive women

**Name:** Rapid tests HBe Ag

**Type:** DEVICE

### Outcomes Module

#### Other Outcomes

**Measure:** Process and acceptability of the drug's intervention

**Time Frame:** Enrollement

**Measure:** Proportion of women with viral load > 6 Log among those HBe Ag negative

**Time Frame:** Enrollement

**Measure:** Proportion of new-born with positive HBs Ag at 6 months according to treatment duration, initial and delivery viral load level

**Time Frame:** 6 months post-partum

**Measure:** Decrease curve of HBV VL after TDF initiation over time

**Time Frame:** From enrollement to 8 weeks or 6 months post-partum

**Measure:** Occurrence of maternal adverse events including serious adverse events and adverse events grade 3 or 4

**Time Frame:** From enrollement to 6 months post-partum

**Measure:** Proportion of women needing treatment continuation in post-partum among those to whom treatment was initiated

**Time Frame:** 6 weeks post-partum

**Measure:** Occurrence of acute exacerbation after treatment interruption

**Time Frame:** From 8 weeks post-partum to 6 months post-partum

#### Primary Outcomes

**Description:** The proportion will be estimated by HBs Ag positivity

**Measure:** Proportion of active HBV infection in new-born at 6 months of life

**Time Frame:** 6 months post-partum

#### Secondary Outcomes

**Description:** Proportion of women with screening proposed among those eligible in antenatal consultation (ANC)

**Measure:** Process and acceptability of the screening phase

**Time Frame:** Enrollement

**Description:** Proportion of women with a done screening among those to whom screening was proposed

**Measure:** Process and acceptability of the screening phase

**Time Frame:** Enrollement

**Description:** Proportion of women with a given results in less than one day among those to whom the test was made

**Measure:** Process and acceptability of the screening phase

**Time Frame:** Enrollement

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

**Measure:** Process and acceptability of the screening phase

**Time Frame:** Enrollement

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 50 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Kampong Cham

**Country:** Cambodia

**Facility:** Kampong Cham Provincial Hospital

**Location 2:**

**City:** Phnom Penh

**Country:** Cambodia

**Facility:** Calmette Hospital

**Location 3:**

**City:** Phnom Penh

**Country:** Cambodia

**Facility:** National Mother and Child Health Center

#### Overall Officials

**Official 1:**

**Affiliation:** Calmette Hospital

**Name:** Samsorphea CHHUN, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** 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.

**PMID:** 35643089

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000008107

- Term: Liver Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000006525

- Term: Hepatitis, Viral, Human

- ID: D000014777

- Term: Virus Diseases

- ID: D000007239

- Term: Infections

- ID: D000004769

- Term: Enterovirus Infections

- ID: D000010850

- Term: Picornaviridae Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000086982

- Term: Blood-Borne Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000018347

- Term: Hepadnaviridae Infections

- ID: D000004266

- Term: DNA Virus Infections

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000006521

- Term: Hepatitis, Chronic

- ID: D000002908

- Term: Chronic Disease

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9592

- Name: Hepatitis A

- Relevance: HIGH

- As Found: Hepatitis

- ID: M9595

- Name: Hepatitis B

- Relevance: HIGH

- As Found: Hepatitis B

- ID: M21609

- Name: Hepatitis B, Chronic

- Relevance: HIGH

- As Found: Hepatitis B Chronic

- ID: M9591

- Name: Hepatitis

- Relevance: HIGH

- As Found: Hepatitis

- ID: M2664

- Name: Persistent Infection

- Relevance: HIGH

- As Found: Chronic Infection

- ID: M11107

- Name: Liver Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9610

- Name: Hepatitis, Viral, Human

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7930

- Name: Enterovirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M13745

- Name: Picornaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M2593

- Name: Blood-Borne Infections

- Relevance: LOW

- As Found: Unknown

- ID: M20487

- Name: Hepadnaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M7442

- Name: DNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M9607

- Name: Hepatitis, Chronic

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006506

- Term: Hepatitis A

- ID: D000006509

- Term: Hepatitis B

- ID: D000088562

- Term: Persistent Infection

- ID: D000019694

- Term: Hepatitis B, Chronic

- ID: D000006505

- Term: Hepatitis

### Intervention Browse Module - Ancestors

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000018894

- Term: Reverse Transcriptase Inhibitors

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000019380

- Term: Anti-HIV Agents

- ID: D000044966

- Term: Anti-Retroviral Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M296

- Name: Tenofovir

- Relevance: HIGH

- As Found: Working

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20935

- Name: Reverse Transcriptase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21350

- Name: Anti-HIV Agents

- Relevance: LOW

- As Found: Unknown

- ID: M25428

- Name: Anti-Retroviral Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000068698

- Term: Tenofovir

### Misc Info Module

- Version Holder: 2024-05-24
