Trial Outcomes & Findings for Arresting Vertical Transmission of Hepatitis B Virus (NCT NCT03567382)
NCT ID: NCT03567382
Last Updated: 2021-02-24
Results Overview
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%.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
179 participants
Primary outcome timeframe
Upon completion of the exit survey, or up to 12 months
Results posted on
2021-02-24
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
Infants Born to High-risk Mothers
Infants born to mothers with high-risk HBV
|
Infants Born to Low-risk Mothers
Infants born to mothers with low-risk HBV
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
81
|
9
|
79
|
|
Overall Study
Received Tenofovir
|
9
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
7
|
46
|
7
|
46
|
|
Overall Study
NOT COMPLETED
|
3
|
35
|
2
|
33
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
Infants Born to High-risk Mothers
Infants born to mothers with high-risk HBV
|
Infants Born to Low-risk Mothers
Infants born to mothers with low-risk HBV
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
21
|
1
|
21
|
|
Overall Study
Withdrawal by Subject
|
2
|
14
|
1
|
12
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
High-risk Mothers
n=10 Participants
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.
|
Low-risk Mothers
n=81 Participants
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.
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
24.4 years
STANDARD_DEVIATION 5.4 • n=10 Participants
|
30.59 years
STANDARD_DEVIATION 5.47 • n=81 Participants
|
29.91 years
STANDARD_DEVIATION 5.77 • n=91 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=10 Participants
|
81 Participants
n=81 Participants
|
91 Participants
n=91 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=10 Participants
|
0 Participants
n=81 Participants
|
0 Participants
n=91 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Congo, The Democratic Republic of the
|
10 Participants
n=10 Participants
|
81 Participants
n=81 Participants
|
91 Participants
n=91 Participants
|
|
Gestational age at enrollment, Continuous
|
20.8 weeks
STANDARD_DEVIATION 3.55 • n=10 Participants
|
17.54 weeks
STANDARD_DEVIATION 4.65 • n=81 Participants
|
17.91 weeks
STANDARD_DEVIATION 4.64 • n=91 Participants
|
|
Total pregnancies, Continuous
|
2.7 pregnancies
STANDARD_DEVIATION 2.06 • n=10 Participants
|
3.52 pregnancies
STANDARD_DEVIATION 2.01 • n=81 Participants
|
3.43 pregnancies
STANDARD_DEVIATION 2.02 • n=91 Participants
|
|
Number of living children, Continuous
|
0.89 living children
STANDARD_DEVIATION 1.54 • n=10 Participants
|
2.25 living children
STANDARD_DEVIATION 1.80 • n=81 Participants
|
2.10 living children
STANDARD_DEVIATION 1.82 • n=91 Participants
|
|
Marital status, Categorical
Married
|
7 Participants
n=10 Participants
|
66 Participants
n=81 Participants
|
73 Participants
n=91 Participants
|
|
Marital status, Categorical
Divorced
|
0 Participants
n=10 Participants
|
1 Participants
n=81 Participants
|
1 Participants
n=91 Participants
|
|
Marital status, Categorical
Separated
|
0 Participants
n=10 Participants
|
1 Participants
n=81 Participants
|
1 Participants
n=91 Participants
|
|
Marital status, Categorical
Never Married
|
2 Participants
n=10 Participants
|
13 Participants
n=81 Participants
|
15 Participants
n=91 Participants
|
|
Marital status, Categorical
Missing
|
1 Participants
n=10 Participants
|
0 Participants
n=81 Participants
|
1 Participants
n=91 Participants
|
|
Highest Education, Categorical
Primary
|
1 Participants
n=10 Participants
|
1 Participants
n=81 Participants
|
2 Participants
n=91 Participants
|
|
Highest Education, Categorical
Secondary
|
6 Participants
n=10 Participants
|
59 Participants
n=81 Participants
|
65 Participants
n=91 Participants
|
|
Highest Education, Categorical
Higher education
|
3 Participants
n=10 Participants
|
17 Participants
n=81 Participants
|
20 Participants
n=91 Participants
|
|
Highest Education, Categorical
Missing
|
0 Participants
n=10 Participants
|
4 Participants
n=81 Participants
|
4 Participants
n=91 Participants
|
PRIMARY outcome
Timeframe: Upon completion of the exit survey, or up to 12 monthsPopulation: 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.
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%.
Outcome measures
| Measure |
High-risk Mothers
n=7 Participants
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.
|
Low-risk Mothers
n=46 Participants
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.
|
|---|---|---|
|
Number of Participants With Lab Testing Acceptability Survey Scores >80%
Testing for Mothers
|
7 Participants
|
41 Participants
|
|
Number of Participants With Lab Testing Acceptability Survey Scores >80%
Testing for Infants
|
7 Participants
|
40 Participants
|
PRIMARY outcome
Timeframe: Upon completion of the exit survey, or up to 12 monthsPopulation: 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.
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%.
Outcome measures
| Measure |
High-risk Mothers
n=7 Participants
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.
|
Low-risk Mothers
n=46 Participants
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.
|
|---|---|---|
|
Number of Mothers With Infant Vaccination Acceptability Survey Scores >80%
|
7 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: Measured at 6 months after birthPopulation: 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.
Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life.
Outcome measures
| Measure |
High-risk Mothers
n=7 Participants
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.
|
Low-risk Mothers
n=46 Participants
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.
|
|---|---|---|
|
Number of Infants With HBV Positivity at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
High-risk Mothers
n=9 Participants
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.
|
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.
|
|---|---|---|
|
Number of Mothers With High-risk HBV Demonstrating Adherence to Tenofovir Therapy
|
9 Participants
|
—
|
SECONDARY outcome
Timeframe: Within 24 hours after birthTimeliness of infant HBV vaccination is defined as \>90% of infants receiving birth dose vaccine within 24 hours of life
Outcome measures
| Measure |
High-risk Mothers
n=9 Participants
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.
|
Low-risk Mothers
n=79 Participants
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.
|
|---|---|---|
|
Number of Infants Receiving Timely Birth Dose Vaccination
|
8 Participants
|
38 Participants
|
Adverse Events
High-risk Mothers
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Low-risk Mothers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Infants Born to High-risk Mothers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Infants Born to Low-risk Mothers
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
High-risk Mothers
n=10 participants at risk
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.
|
Low-risk Mothers
n=81 participants at risk
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.
|
Infants Born to High-risk Mothers
n=9 participants at risk
Infants born to mothers with high-risk HBV
|
Infants Born to Low-risk Mothers
n=79 participants at risk
Infants born to mothers with low-risk HBV
|
|---|---|---|---|---|
|
Hepatobiliary disorders
Rebound elevation of ALT and HBV DNA after discontinuation of Tenofovir
|
20.0%
2/10 • Number of events 2 • The participants were monitored for adverse events over the duration of treatment (an average of 6 months for High-risk Mothers taking tenofovir therapy, and an average of 3 days or the duration of hospital stay for infants after receiving hepatitis B vaccination). Since Low-risk Mothers did not receive a study intervention, adverse event data was not overtly sought unless self-reported by participant.
|
0.00%
0/81 • The participants were monitored for adverse events over the duration of treatment (an average of 6 months for High-risk Mothers taking tenofovir therapy, and an average of 3 days or the duration of hospital stay for infants after receiving hepatitis B vaccination). Since Low-risk Mothers did not receive a study intervention, adverse event data was not overtly sought unless self-reported by participant.
|
0.00%
0/9 • The participants were monitored for adverse events over the duration of treatment (an average of 6 months for High-risk Mothers taking tenofovir therapy, and an average of 3 days or the duration of hospital stay for infants after receiving hepatitis B vaccination). Since Low-risk Mothers did not receive a study intervention, adverse event data was not overtly sought unless self-reported by participant.
|
0.00%
0/79 • The participants were monitored for adverse events over the duration of treatment (an average of 6 months for High-risk Mothers taking tenofovir therapy, and an average of 3 days or the duration of hospital stay for infants after receiving hepatitis B vaccination). Since Low-risk Mothers did not receive a study intervention, adverse event data was not overtly sought unless self-reported by participant.
|
Additional Information
Peyton Thompson, MD, MSCR
University of North Carolina at Chapel Hill
Phone: 919-445-0854
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place