Trial Outcomes & Findings for Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand (NCT NCT01745822)

NCT ID: NCT01745822

Last Updated: 2021-03-05

Results Overview

Infection is defined as a HBsAg positive test confirmed by detectable HBV DNA

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

654 participants

Primary outcome timeframe

6 months of age

Results posted on

2021-03-05

Participant Flow

Study Enrollment Dates: January 8, 2013 to August 19, 2015 in 17 hospital based antenatal care and pediatrics departments in Thailand

Participant milestones

Participant milestones
Measure	Tenofovir Disoproxil Fumarate tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Overall Study STARTED	331	323
Overall Study COMPLETED	331	323
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tenofovir Disoproxil Fumarate n=168 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=163 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Total n=331 Participants Total of all reporting groups
Age, Continuous	25.5 years n=5 Participants	26.7 years n=7 Participants	26.1 years n=5 Participants
Sex: Female, Male Female	168 Participants n=5 Participants	163 Participants n=7 Participants	331 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	168 Participants n=5 Participants	163 Participants n=7 Participants	331 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Gestational age at enrollment	28.3 weeks n=5 Participants	28.1 weeks n=7 Participants	28.3 weeks n=5 Participants

PRIMARY outcome

Timeframe: 6 months of age

Population: Participants in the primary analysis

Infection is defined as a HBsAg positive test confirmed by detectable HBV DNA

Outcome measures

Outcome measures
Measure	Tenofovir Disoproxil Fumarate n=147 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=147 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Percentage of Infants With Hepatitis B Infection at 6 Months of Age	0 Participants	3 Participants

SECONDARY outcome

Timeframe: from enrollment (28 weeks' gestation) to 12 months postpartum

Population: Mother-infant pairs

Occurrence of maternal and infant adverse events, including maternal and infants Serious Adverse Events (as defined by the International Conference on Harmonization Good Clinical Practice) and NIH Division of AIDS grade 3/4 signs and symptoms, regardless of their relatedness to the study treatment.

Outcome measures

Outcome measures
Measure	Tenofovir Disoproxil Fumarate n=329 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=323 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Percentage of Participants With Adverse Events Maternal	41 Participants	44 Participants
Percentage of Participants With Adverse Events Infant	43 Participants	38 Participants

SECONDARY outcome

Timeframe: Following planned discontinuation of study treatment up to 12 months postpartum

Population: Women who had delivered

Flare, or acute exacerbation of hepatitis B, after study treatment interruption is defined as an Alanine Aminotransferase plasma level above 300 IU/mL

Outcome measures

Outcome measures
Measure	Tenofovir Disoproxil Fumarate n=154 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=157 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Percentage of Participants With Flares After Study Treatment Interruption	9 Participants	5 Participants

SECONDARY outcome

Timeframe: at or after 6 months through 12 months of age

Population: infants until 12 months of age

Infants will be considered HBV infected if at any time point at or after 6 months through 12 months of age, a sample tests positive for HBsAg and HBV DNA

Outcome measures

Outcome measures
Measure	Tenofovir Disoproxil Fumarate n=147 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=147 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Percentage of Infants With Hepatitis B Infection at or After 6 Months Through 12 Months of Age	0 Participants	3 Participants

SECONDARY outcome

Timeframe: assessed at 6 months and 12 months of age, 6 months reported

Population: infants at 6 months of age

Weight, length/height and head circumference WHO Z scores are measures of relative weight, height and head circumference adjusted for child age and sex. The Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean.

Outcome measures

Outcome measures
Measure	Tenofovir Disoproxil Fumarate n=148 Participants tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=146 Participants matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Weight, Height and Head Circumference for Age Weight for age	-0.4 Z-score Standard Deviation 1.1	-0.2 Z-score Standard Deviation 1.1
Weight, Height and Head Circumference for Age Length for age	-0.2 Z-score Standard Deviation 1.2	-0.2 Z-score Standard Deviation 1.2
Weight, Height and Head Circumference for Age Head circumference for age	-0.6 Z-score Standard Deviation 1.1	-0.6 Z-score Standard Deviation 0.9

Adverse Events

Tenofovir Disoproxil Fumarate

Serious events: 62 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 66 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gonzague Jourdain

French National Research Institute for Sustainable Development (IRD)

Phone: +66818830065

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tenofovir Disoproxil Fumarate n=331 participants at risk tenofovir disoproxil fumarate, 300 mg tablets tenofovir disoproxil fumarate: administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum	Placebo n=323 participants at risk matching placebo (of tenofovir disoproxil fumarate) placebo: administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Blood and lymphatic system disorders Anaemia	1.8% 6/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.62% 2/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Blood and lymphatic system disorders Lymphopenia	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.00% 0/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Blood and lymphatic system disorders Neutropenia	0.60% 2/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Congenital, familial and genetic disorders Persistent foetal circulation	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Hepatobiliary disorders Jaundice	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Infections and infestations Meningitis	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Infections and infestations Urinary tract infection	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Investigations Alanine aminotransferase increased	7.3% 24/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	5.0% 16/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Investigations Aspartate aminotransferase increased	0.91% 3/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.93% 3/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Investigations Blood phosphorus decreased	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.62% 2/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Investigations Neutrophil count abnormal	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Nervous system disorders Cerebral atrophy	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.00% 0/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Pregnancy, puerperium and perinatal conditions Breech presentation	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Pregnancy, puerperium and perinatal conditions Low birth weight baby	0.60% 2/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.62% 2/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Pregnancy, puerperium and perinatal conditions Postpartum haemorrhage	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.00% 0/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Pregnancy, puerperium and perinatal conditions Premature baby	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Pregnancy, puerperium and perinatal conditions Retained placenta or membranes	0.30% 1/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.00% 0/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/331 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.	0.31% 1/323 • From enrollment (28 weeks' gestation) to 12 months postpartum Adverse event information was collected using the same definitions of adverse event and serious adverse event as the clinicaltrials.gov definitions. Only serious adverse events and other (not including serious) Grade 3 or 4 adverse events are reported.