Hepatitis B, Vertical Transmission of Infectious Disease
Conditions
Brief summary
The purpose of this pilot study is to demonstrate the feasibility of adding HBV screening and treatment of pregnant women to the existing HIV PMTCT platform in order to prevent mother-to-child transmission of hepatitis B virus.
Detailed description
Hepatitis B virus (HBV) is a leading cause of chronic liver disease globally, with devastating complications such as cirrhosis, hepatocellular carcinoma and death. Vertical transmission (VT) of HBV is a worldwide public health concern because infected children are at high risk of developing chronic liver disease. It is a particular problem in the Democratic Republic of the Congo (DRC); preliminary data suggest that approximately 3% of children have HBV infection due to VT. However, VT is preventable. Pregnant women with risk factors can be identified and treatments given which can virtually eliminate transmission. Unfortunately, despite the high burden of HBV, neither HBV testing of pregnant women nor interventions to prevent HBV VT are routinely performed in the DRC and elsewhere in sub-Saharan Africa. This pilot feasibility study will address this healthcare gap by identifying women with HBV early in their pregnancies and intervening to prevent VT by (1) treating mothers with high-risk HBV (defined as HBeAg positivity and/or HBV viremia \>10\^6) with tenofovir and (2) providing HBV vaccine to HBV-exposed infants within 24 hours of birth. This pilot study will piggyback onto an existing study that is evaluating the DRC's HIV Prevention of Maternal-to-Child Transmission Option B+ (PMTCT+) strategy. Combining programs to prevent VT of HBV and HIV enables using the same personnel and infrastructure to implement both interventions. Furthermore, tenofovir, used to treat HBV infections, is already used in the DRC to treat HIV. Researchers hypothesize that utilizing the existing PMTCT+ infrastructure in the DRC will provide a cost-effective platform to prevent HBV VT. If effective, this model of treatment will inform future public health efforts and wider policy recommendations that can be applied in the DRC and throughout the Sub-Saharan African region to reduce the burden of HBV.
Interventions
DRUGTenofovir Disoproxil Fumarate
300 mg tablet of TDF once daily from 28-32 weeks gestation through 12 weeks postpartum.
BIOLOGICALMonovalent HBV vaccine
Infants born to HBsAg-positive women will be given a single dose of monovalent HBV vaccine within 24 hours of life.
Sponsors
Kinshasa School of Public Health
Ohio State University
University of North Carolina, Chapel Hill
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Pregnant women receiving care at Binza and Kingasani maternity centers presenting prior to 24 weeks gestation * Infants born to HBV-positive women
Exclusion criteria
* Participants who are severely sick and who require prolonged hospitalization. * Any women who do not intend to stay in Kinshasa for prenatal care through delivery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Lab Testing Acceptability Survey Scores >80% | Upon completion of the exit survey, or up to 12 months | The acceptability of laboratory testing approach to participants will be defined as \>80% acceptability on a two questions each measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for participant responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to take my blood. Scores equal to or greater than 4 considered 80%. |
| Number of Mothers With Infant Vaccination Acceptability Survey Scores >80% | Upon completion of the exit survey, or up to 12 months | The acceptability of the intervention approach to participants will be defined as \>80% acceptability on a single question measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to vaccinate my infant. Scores equal to or greater than 4 considered 80%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infants Receiving Timely Birth Dose Vaccination | Within 24 hours after birth | Timeliness of infant HBV vaccination is defined as \>90% of infants receiving birth dose vaccine within 24 hours of life |
| Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV | Measured at 6 months after birth | Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life. |
| Number of Mothers With High-risk HBV Demonstrating Adherence to Tenofovir Therapy | Pill counts to be measured monthly. Total adherence averaged over 6-month treatment period. | Adherence to tenofovir therapy is defined as \<20% of pills remaining on monthly pill counts for high-risk mothers with HBV receiving tenofovir |
Countries
Democratic Republic of the Congo
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-risk Mothers Mothers with high-risk HBV (defined as viral load \>10\^6 and/or HBeAg positivity) will be treated with tenofovir disoproxil fumarate (TDF) to further reduce the risk of vertical transmission of HBV. All HBV-exposed infants (regardless of mother's status of high- or low-risk HBV) will receive monovalent HBV vaccine within 24 hours of life.
Tenofovir Disoproxil Fumarate: 300 mg tablet of TDF once daily from 28-32 weeks gestation through 12 weeks postpartum.
Monovalent HBV vaccine: Infants born to HBsAg-positive mothers will be given a single dose of monovalent HBV vaccine within 24 hours of life. | 10 |
| Low-risk Mothers Mothers with low risk HBV (defined as a viral load \<10\^6 and negative HBeAg) will not receive tenofovir disoproxil fumarate therapy during or after pregnancy. Their infants will still receive monovalent HBV vaccine within 24 hours of life.
Monovalent HBV vaccine: Infants born to HBsAg-positive mothers will be given a single dose of monovalent HBV vaccine within 24 hours of life. | 81 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 21 | 1 | 21 |
| Overall Study | Withdrawal by Subject | 2 | 14 | 1 | 12 |
Baseline characteristics
| Characteristic | High-risk Mothers | Low-risk Mothers | Total |
|---|---|---|---|
| Age, Continuous | 24.4 years STANDARD_DEVIATION 5.4 | 30.59 years STANDARD_DEVIATION 5.47 | 29.91 years STANDARD_DEVIATION 5.77 |
| Gestational age at enrollment, Continuous | 20.8 weeks STANDARD_DEVIATION 3.55 | 17.54 weeks STANDARD_DEVIATION 4.65 | 17.91 weeks STANDARD_DEVIATION 4.64 |
| Highest Education, Categorical Higher education | 3 Participants | 17 Participants | 20 Participants |
| Highest Education, Categorical Missing | 0 Participants | 4 Participants | 4 Participants |
| Highest Education, Categorical Primary | 1 Participants | 1 Participants | 2 Participants |
| Highest Education, Categorical Secondary | 6 Participants | 59 Participants | 65 Participants |
| Marital status, Categorical Divorced | 0 Participants | 1 Participants | 1 Participants |
| Marital status, Categorical Married | 7 Participants | 66 Participants | 73 Participants |
| Marital status, Categorical Missing | 1 Participants | 0 Participants | 1 Participants |
| Marital status, Categorical Never Married | 2 Participants | 13 Participants | 15 Participants |
| Marital status, Categorical Separated | 0 Participants | 1 Participants | 1 Participants |
| Number of living children, Continuous | 0.89 living children STANDARD_DEVIATION 1.54 | 2.25 living children STANDARD_DEVIATION 1.8 | 2.10 living children STANDARD_DEVIATION 1.82 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Congo, The Democratic Republic of the | 10 Participants | 81 Participants | 91 Participants |
| Sex: Female, Male Female | 10 Participants | 81 Participants | 91 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Total pregnancies, Continuous | 2.7 pregnancies STANDARD_DEVIATION 2.06 | 3.52 pregnancies STANDARD_DEVIATION 2.01 | 3.43 pregnancies STANDARD_DEVIATION 2.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 81 | 0 / 9 | 1 / 79 |
| other Total, other adverse events | 2 / 10 | 0 / 81 | 0 / 9 | 0 / 79 |
| serious Total, serious adverse events | 0 / 10 | 0 / 81 | 0 / 9 | 0 / 79 |
Outcome results
Primary
Number of Mothers With Infant Vaccination Acceptability Survey Scores >80%
The acceptability of the intervention approach to participants will be defined as \>80% acceptability on a single question measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to vaccinate my infant. Scores equal to or greater than 4 considered 80%.
Time frame: Upon completion of the exit survey, or up to 12 months
Population: There were a total of 53 mothers (7 high-risk and 46 low-risk) who completed the 6-month study visit, thus this is the total number of mothers who completed the exit survey. One survey was completed per mother/infant dyad.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-risk Mothers | Number of Mothers With Infant Vaccination Acceptability Survey Scores >80% | 7 Participants |
| Low-risk Mothers | Number of Mothers With Infant Vaccination Acceptability Survey Scores >80% | 42 Participants |
Primary
Number of Participants With Lab Testing Acceptability Survey Scores >80%
The acceptability of laboratory testing approach to participants will be defined as \>80% acceptability on a two questions each measured using a 5-point Likert scale (range 1-5, highest score of 5 representing the highest acceptability). For example, the options for participant responses will include: Very unacceptable (1), Somewhat unacceptable (2), No opinion (3), Somewhat acceptable (4), Very acceptable (5) and Did not allow study personnel to take my blood. Scores equal to or greater than 4 considered 80%.
Time frame: Upon completion of the exit survey, or up to 12 months
Population: There were a total of 53 mothers (7 high-risk and good 46 low-risk) who completed the 6-month study visit, thus this is the total number of mothers who completed the exit survey. One survey was completed per mother/infant dyad.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High-risk Mothers | Number of Participants With Lab Testing Acceptability Survey Scores >80% | Testing for Mothers | 7 Participants |
| High-risk Mothers | Number of Participants With Lab Testing Acceptability Survey Scores >80% | Testing for Infants | 7 Participants |
| Low-risk Mothers | Number of Participants With Lab Testing Acceptability Survey Scores >80% | Testing for Mothers | 41 Participants |
| Low-risk Mothers | Number of Participants With Lab Testing Acceptability Survey Scores >80% | Testing for Infants | 40 Participants |
Secondary
Number of Infants Receiving Timely Birth Dose Vaccination
Timeliness of infant HBV vaccination is defined as \>90% of infants receiving birth dose vaccine within 24 hours of life
Time frame: Within 24 hours after birth
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-risk Mothers | Number of Infants Receiving Timely Birth Dose Vaccination | 8 Participants |
| Low-risk Mothers | Number of Infants Receiving Timely Birth Dose Vaccination | 38 Participants |
Secondary
Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV
Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life.
Time frame: Measured at 6 months after birth
Population: A total of 88 infants were born to mothers in the study, but only 53 infants (7 born to high-risk mothers and 46 born to low-risk mothers) were followed through 6 months of life and tested for HBsAg at that time.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-risk Mothers | Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV | 0 Participants |
| Low-risk Mothers | Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV | 0 Participants |
Secondary
Number of Mothers With High-risk HBV Demonstrating Adherence to Tenofovir Therapy
Adherence to tenofovir therapy is defined as \<20% of pills remaining on monthly pill counts for high-risk mothers with HBV receiving tenofovir
Time frame: Pill counts to be measured monthly. Total adherence averaged over 6-month treatment period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High-risk Mothers | Number of Mothers With High-risk HBV Demonstrating Adherence to Tenofovir Therapy | 9 Participants |