Clinical trial NCT04998838: Stop Hep B @ Birth
Official title: Stop Hep B @ Birth: Community-Oriented Care Model for the Prevention of Mother-To-Child Transmission of Hepatitis B in Peri-Urban Yangon
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatitis B
Lead sponsor: Myanmar Liver Foundation
Sponsor class: OTHER
First posted: 2021-08-10
Enrollment: 110
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Antenatal screening for HBV, anti-viral treatment with tenofovir according to treatment eligibility criteria, and birth dose vaccination at delivery to prevent mother-to-child transmission of HBV
Primary purpose: PREVENTION

Brief summary: Single arm, prospective open-label study of a care model consisting of two components: Component I aims to achieve high coverage of interventions to prevent maternal-to-child transmission of hepatitis B virus: antenatal tenofovir, and timely newborn administration of hepatitis B birth dose vaccine and hepatitis B immune globulin; Component II aims to achieve high coverage of screening, vaccination, and anti-viral therapy for HBV among household members of women with chronic HBV infection.

Detailed description: An estimated 248 million people worldwide are chronically infected with hepatitis B virus (HBV); and 75% of them live in Asia. Mother-to-child transmission (MTCT) accounts for the majority of chronic hepatitis B infections in Southeast Asia. Elimination of MTCT of HBV is theoretically possible with a comprehensive suite of interventions that includes birth dose vaccination, hepatitis B immune globulin, and antenatal antiviral therapy (e.g., tenofovir). However, the ideal gestational age to initiate antenatal tenofovir remains undefined; and evidence is lacking for implementation strategies capable of providing cost-effective, equitable access to a comprehensive suite of interventions to prevent MTCT of HBV in low-resource settings.

Component I: Prevention of Vertical Transmission Pregnant women living in the study area will be identified and screened for hepatitis B by a network of antenatal care (ANC) providers and existing community outreach workers; HBsAg positive patients will be invited to participate in the study. Consenting participants will provide serum samples to assess eligibility for anti-viral therapy: creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count, HCV, HIV. Pregnant women eligible for antiviral therapy according to WHO criteria, or who have viral load (VL) \>200,000 IU/mL, will be treated with tenofovir starting at 20 weeks gestation through 4 weeks postpartum. Hospital-based delivery will be encouraged. All newborns, including those delivered at home, will receive the HBV birth dose vaccine within 24 hours of delivery, and newborns of women on tenofovir treatment will also receive Hepatitis B Immunoglobulin within 24 hours after delivery. Children will be linked to routine immunization services in Myanmar to complete their HBV vaccination series (HBV is co-formulated in a pentavalent vaccine). Maternal VL will be measured at delivery; infants will be tested for hepatitis B infection at 24-28 weeks postpartum.

Component II -- Household Screening and Treatment The household members of HBsAg positive pregnant women who consent to participate in the study will be screened for HBV-related immune status and chronic HBV infection. Non-immune individuals (HBsAb/Ag negative) will be vaccinated; HBsAg positive household members will be assessed for treatment eligibility and initiated on anti-viral therapy according to World Helath Organization guidelines. Eligible household members will also be screened every six months for hepatocellular carcinoma (HCC) by liver ulatrasound and alpha-fetoprotein levels

Qualitative Study:

In-depth interviews with approximately 30 HBsAg-positive women, 30 HBVsAg-negative women, and 20 household members of study participants will be conducted to assess barriers and facilitators related to HBV testing and treatment. Approximately 15 key-informant interviews with healthcare providers and community leaders will also be conducted. Sample size will depend on data saturation and will be adjusted based on results of data analysis during the study.

Eligibility criteria: Inclusion Criteria:

* Pregnant women \>= 18 years of age
* Gestational age =\<34 weeks
* Test positive for HBsAg
* Live in study site area in South Dagon and Dagon Seikkan Townships, Yangon Region
* Give informed consent to participate in the study
* Newborns and household members of pregnant women enrolled in the study according to previous inclusion criteria

Exclusion Criteria:

* Alanine aminotransferase (ALT) levels \>300 IU/L

For qualitative study:

Inclusion criteria

* Key informants (e.g., healthcare providers and community leaders in the study area) OR
* HBsAg+ women and their household members in the study area
* HBsAg- women and their household members in the stud area
* Give informed consent to participate in the study
* History of renal dysfunction
* CrCL \< 50mL/min
* ALT\>5 times the upper limit of normal (ULN)
* Evidence of decompensated cirrhosis (e.g., jaundice, ascites, history of upper gastrointestinal bleeding/esophageal varices, and hepatic encephalopathy)
* Any concomitant condition or treatment that, in view of the clinical site investigator, would contraindicate participation or satisfactory follow-up in the study HIV positive status unless 1) they are currently on additional ART therapy, or 2) their viral load is demonstrated to be \<50 copies. Women who are newly diagnosed with HIV and referred to start a TDF-based regimen may be considered eligible once they have started the TDF-based regimen.
* Concurrent participation in any other clinical trial without written agreement of the study team
* Does not intend to deliver within catchment area, and/or intends to migrate before newborn follow-up is complete

Primary outcomes:
measure: Vaccine within 24 hours
timeFrame: Within 24 hours of birth
measure: Effective treatment of pregnant women
timeFrame: During pregnancy (until delivery) of each woman, average of 9 months
measure: Household contact screening
timeFrame: Upon identification of participating women, until the end of the project, average of 1 year
Secondary outcomes:
measure: Total screening of mothers
timeFrame: During pregnancy (until delivery) of each woman, average of 9 months
measure: Antenatal care for HBV positive pregnant mothers
timeFrame: During pregnancy (until delivery) of each woman, average of 9 months
measure: Vaccination of HBV negative pregnant mothers
timeFrame: During pregnancy (until delivery) of each woman, average of 9 months
measure: Treatment of high viral load pregnant mothers
timeFrame: At delivery; during antenatal care testing; at 4 months postpartum, throughout the project, average of 12 months
measure: Viral suppression
timeFrame: At delivery, throughout the project (one off)
measure: Mother-to-child transmission
timeFrame: At 28 weeks postpartum, throughout the project (one off)
measure: Household screening
timeFrame: At household screening, throughout the project (one off)
Other outcomes:
measure: Completed vaccination courses
timeFrame: Before age 1, average of 1 year
measure: Proportion of pregnant women with HBsAg identified by surveillance team members
timeFrame: During pregnancy, average of 9 months
measure: Timeliness of pregnancy surveillance
timeFrame: During pregnancy, average of 9 months
measure: Equity of intervention
timeFrame: During pregnancy and in first year after delivery, average of 16 months
Locations:
city: Yangon
country: Myanmar
facility: BK Kee Clinic
Study officials:
affiliation: Myanmar Liver Foundation
name: Khin Phone Kyi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Adam K Richards, MD
role: PRINCIPAL_INVESTIGATOR
References: