Clinical trial NCT04029454: Neovac 2 Burkina Faso: Impact of the Integration of Hepatitis B Birth Dose Vaccine Into the Infant Immunization Schedule
Official title: Neovac 2 Burkina Faso: Impact of the Integration of Hepatitis B Birth Dose Vaccine Into the Infant Immunization Schedule: a Mixed Methods Study Including a Cluster-randomized Trial, an Anthropological Study and an Economic Evaluation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatitis B
Keywords: Infectious Disease Transmission, Vertical
immunization programs
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
Collaborators: name: Agence de Médecine Préventive, France
name: Centre Muraz
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Gilead Sciences
name: Abbott
First posted: 2019-07-23
Enrollment: 10000
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Pragmatic Stepped-wedge cluster randomized trial
Primary purpose: PREVENTION

Brief summary: Hepatitis B virus (HBV) infection is an important global health problem, and the WHO adopted a strategy to eliminate HBV infection as a public health threat by the year 2030. In order to eliminate, it is critical to prevent the mother-to-child transmission (MTCT) of hepatitis B. Since 2009, the WHO recommends to administer hepatitis B vaccine within 24 hours of birth to prevent MTCT.2 However, in Africa, the majority of countries provide hepatitis B vaccine as a combined vaccine (pentavalent or hexavalent) at the age of 6-10-14 weeks or 8-12-16 weeks after the birth, and only 10 sub-Saharan African countries integrated birth dose vaccine into their national immunization program. This is because, the GAVI, the Vaccine Alliance, does not support monovalent hepatitis B vaccine, and also about half of babies in Africa are born at home without the immediate access to vaccination. Moreover, the evidence base to support this WHO's recommendation to start immunizing immediately at birth, rather than later at 6-8 weeks of life, is not strong.

Through a multidisciplinary approach comprising epidemiological, anthropological and economic components, the primary objective of the study is to measure the impact of the introduction of birth dose hepatitis B vaccine into the infant immunization program in Burkina Faso.

Expected results will be to develop strong evidence base (effectiveness \& cost-effectiveness) to recommend the integration of birth dose hepatitis B vaccine into the current vaccination schedule (8-12-16 weeks as a combined vaccine), to facilitate the Burkinabé Government to include the birth dose hepatitis B vaccine in their national vaccination program, to inform other African countries which have not yet integrated the birth dose hepatitis B vaccine in their national program and to imply whether additional strategy (e.g., maternal screening and antiviral therapy during pregnancy) might be necessary in order to eliminate the risk of mother-to-child transmission of hepatitis B.

Detailed description: The study combines mixed methods to achieve its aim of evaluating the impact of the introduction of birth dose hepatitis B vaccine into the infant immunisation program in Burkina Faso. It is composed of 4 components:

Workpackage (WP1): Stepped Wedge Cluster randomized controlled trial:

* to measure the impact of the introduction of birth dose hepatitis B vaccine into the infant immunization program on the mother-to-child transmission (primary objective)
* To examine a dose-dependent effect of hepatitis B vaccine (according to the total number of doses from one to four doses)
* To examine a time-dependent effect of the first dose of hepatitis B vaccine
* To study the impact of birth dose vaccine in infants aged at 9 months according to maternal HBsAg and HBeAg status
* To compare immunological responses in both groups by titration of anti-HBs antibodies in children at 9 months
* To describe vaccine coverage and its timeliness of birth dose hepatitis B vaccine and other routine infant vaccines in Burkina Faso
* To estimate the prevalence of HBV infection in mothers of 9-month-old children

WP2: Anthropological study • To evaluate the acceptability of healthcare workers and people in the community about the integration of hepatitis B birth dose vaccine in the infant vaccination program in Burkina Faso

WP3: Economic evaluation

* To evaluate the cost-effectiveness of the integration of hepatitis B birth dose vaccine in the infant vaccination program, compared to the conventional vaccine schedule (8-12-16 weeks) in Burkina Faso
* To evaluate the diagnostic performance of low-cost HBV markers to identify women at high risk of mother-to-child transmission in low-income countries

WP4: Virological evaluation

• To evaluate the diagnostic performance of low-cost HBV markers to identify women at high risk of mother-to-child transmission in low-income countries

All the pregnant women attending the antenatal care in the rural health centres of two health districts (Dafra and Dô) in Hauts Bassins Region in Burkina Faso, and their infants will be asked to participate.

Practical sequence of the cluster randomised trial. Even though the evidence is weak and the implementation has been suboptimal, the WHO currently recommends the universal administration of hepatitis B vaccine at birth. For this reason, a "stepped-wedge" design rather than a parallel group design has been selected. Of 24 rural health centers (Centre de santé et de promotion sociale : CSPS) in the districts of Dafra and Dô, introduce monovalent birth dose vaccine will be introduced in a phased manner on a centre by centre basis until all the 24 CSPSs integrate the birth dose vaccines in the program. The rural area of these districts were selected given the proximity to our collaborative study center (Centre Muraz and AMP in Bobo Dioulasso). One of the 24 centers will be randomly selected as the first one to start integrating the birth dose in the program. Then, four weeks later, the second center will be randomly selected to start providing the birth dose vaccine. This will be continued until all 24 CSPSs integrate birth dose vaccine in the program. At the end, this study design will generate two groups of infants in the study area during the study period: those born in centres which already implemented birth dose vaccine, and those born before the introduction of this vaccine.

Informed consent will be obtained from pregnant women who visited routine antenatal care. Subsequently, babies born in a CSPS which is in the intervention period will receive birth dose vaccine whilst those born in a CSPS which is in the control period will not receive the birth dose. For those born at home in the intervention period will receive the monovalent hepatitis B vaccine at the first contact with CSPS, until 8 weeks after the birth when the first dose of pentavalent vaccine (DPT-Hib-HepB) is scheduled. All the infants, irrespective of study period, will receive three doses of pentavalent vaccine as scheduled in the national immunization program.

Case report forms will be used (CRFs to collect basic demographic data of mothers and infants; time and place of birth; type of vaccines administered and its date Laboratory data: HBsAg for all infants and mothers; HBV DNA, HBeAg, AST/ALT for infants and mothers tested positive for HBsAg; anti-HBs for infants tested negative for HBsAg Paper CRFs filled by healthcare workers will be transferred to the study centre (AMP/Centre Muraz). The data will be entered independently by two operators to electronic database (RedCAP) that will be developed on the secured server of the Institut Pasteur.

The risk of HBV infection (HBsAg-positivity) in infants at the age of 9 months between two groups will be compared using an intention-to-treat analysis, in order to assess the effectiveness of adding birth dose vaccine compared to the current vaccine schedule in preventing the mother-to-child transmission in Burkina Faso. To adjust for the calendar time and clustering in the data, A logistic regression model will fit with random effect for cluster and fixed effect for each step.

Eligibility criteria: Inclusion Criteria:

* Pregnant woman
* Living in the study area
* Visited study health centre for the antenatal care or child delivery
* Provided a written informed consent

Exclusion Criteria:

* Miscarriage, abortion, stillborn, neonatal defect incompatible with life
* Any mother or child condition incompatible with the research activities

Primary outcomes:
measure: Proportion of positive HBV infection in 9-month-old children vaccinated at birth compared to children receiving their first vaccination at 8 weeks.
timeFrame: at 9 months old
Secondary outcomes:
measure: Prevalence rate of HBV infection in pregnancy from HBsAg and HBeAg profiles in mothers of 9-month-old children
timeFrame: at 9 months
measure: Sensibility and specificity of low-cost alternative HBV markers
timeFrame: 9 months after delivery
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: District sanitaire de Dafra
state: Dafra
city: Bobo-Dioulasso
country: Burkina Faso
facility: District sanitaire de Do
state: Do
Study officials:
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