Maternal Therapy With TAF Versus TDF to Prevent Vertical Transmission of Hepatitis B
Real World Study of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate to Prevent Vertical Transmission of Hepatitis B in Mothers With High Viral Load
1 other identifier
observational
450
1 country
11
Brief Summary
Immunoprophylaxis failure of hepatitis B (HBV) remains a concern and has been reported in approximately 10-30% of infants born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA \>6log10 copies/mL (or 200,000 IU/mL) is the major independent risk for mother-to-child transmission (MTCT). Two recent random controlled trial (RCT) studies have shown that the use of Tenofovir Disoproxil Fumarate (TDF) in highly viremic HBsAg positive mothers may safely reduce the rate of MTCT when compared between groups of TDF treated and untreated patients. Tenofovir Alafenamide (TAF) is the successor to TDF, and both drugs have a similar mechanism of action to reduce HBV DNA levels and normalize serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. TAF however, has a better safety profile with less adverse effects to bone mineral density and renal function. The present prospective, double-arm study is to evaluate the non-inferiority in the efficacy and safety of TAF therapy versus TDF therapy in highly viremic mothers and their infants for the prevention of MTCT in the real world setting.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jan 2020
11 active sites
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 6, 2019
CompletedFirst Posted
Study publicly available on registry
December 26, 2019
CompletedStudy Start
First participant enrolled
January 27, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2021
CompletedDecember 29, 2020
December 1, 2020
1.7 years
December 6, 2019
December 25, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Assessment on the Proportion of Infants who are Infected with Hepatitis B at the Age of 28 Weeks in the Two Groups
Compare MTCT rates between the two study groups and demonstrate non-inferiority in efficacy. MTCT rate is defined as the proportion of infants with serum HBV DNA \>20 IU/mL and/or HBsAg positivity at 28 weeks of age.
From the date of birth to the age of 24-28 weeks
Assessment on Congenital Defects and/or Malformation Rates in Each Infant Group for Comparison
The rate of congenital defects and/or malformation rates in infants. Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period. The rate of infant congenital defect/malformation as determined in group A will be compared with that of group B.
from the date of birth to Infant's age of 24-28 weeks
Secondary Outcomes (9)
Assessment on the change in Maternal HBV DNA Levels at Delivery
from gestational week 24-28 week to delivery
Maternal Serological Outcomes During the Study: Percentage of Mothers who Loss/Seroconversion of HBsAg or/and HBeAg During the Study
from gestational week 24-28 week to postpartum week 28
Incidence of Treatment-Emergent Adverse Events in Mothers as Stratified by the CTCAE v 5.0
Gestational week 24-28 until Postpartum Week 28
Incidence of Treatment-Emergent Adverse Events in Infants as Stratified by the CTCAE v 5.0
Delivery until Infant age Week 28
Percentage of Mothers with Alanine transferase (ALT) Levels Within the Normal Limit
Gestational week 24-28 until Postpartum week 28
- +4 more secondary outcomes
Study Arms (2)
Arm (A) TAF Group Comprised of Patients from 11 Centers.
225 consecutive patients will be treated with local standard of care. The antiviral drug Tenofovir Alafenamide (TAF) will be used to treat highly viremic chronic hepatitis B mothers from the gestational week 24-28 of pregnancy to delivery of infant at eleven centers across the People's Republic of China (PRC). Infants will receive hepatitis B vaccine plus HBIg at birth (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24.
Arm (B) TDF Group Comprised of Patients from 11 Centers.
225 consecutive patients will be treated with local standard of care. The antiviral drug Tenofovir Disoproxil Fumarate (TDF) will be used to treat highly viremic chronic hepatitis B mothers from the gestational week 24-28 of pregnancy to delivery of infant at eleven centers across the People's Republic of China (PRC). Infants will receive hepatitis B vaccine plus HBIg at birth (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24.
Interventions
Tenofovir Alafenamide (TAF) will be provided, 25 mg Per Oral daily.
Tenofovir Disoproxil Fumarate (TDF) will be provided, 300 mg Per Oral daily.
Eligibility Criteria
225 consecutive chronically infected hepatitis B mothers who are willing to receive tenofovir alafenamide (TAF) treatment and another consecutive 225 who are willing to receive tenofovir disoproxil fumarate (TDF) treatment at eleven centers across China for high viremic load during pregnancy will be enrolled and followed prospectively for data collection. These patients underwent TAF/TDF treatment in their respective care centers and will be grouped together in Group A for TAF treatment and Group B for TDF treatment for primary and secondary analysis.
You may qualify if:
- Pregnant female, above 18 years of age and under 40 years of age.
- Gestational age between 12-14 weeks (The screening on patients can be started at gestational week 12).
- Documented compensated and stable chronic hepatitis B defined by all of the following:
- HBsAg persistently positive \> 6 months.
- Clinical history, physical findings, and test results are compatible with compensated chronic hepatitis B.
- Detectable maternal serum HBsAg and HBeAg at the screening visit.
- Maternal serum HBV DNA levels exceeding 200,000 IU/mL by the COBAS Amplicor HBV PCR assay at screening visits.
- Patient is willing and able to comply with the study drug regimen and all other study requirements. Patient is also willing to prevent another pregnancy in 28 weeks after delivery of the current baby.
- Patient and her husband (both father and mother of the child) understand the risk and are willing to have the mother participating in the study. The mother must be willing and able to provide written informed consent to participate in the study.
You may not qualify if:
- Patients will be excluded if they have any one of the following:
- Creatinine clearance \<100 mL/min (using the Cockcroft-Gault method based on serum creatinine and ideal body weight) or hypo-phosphoremia (below normal range).
- History of renal events on adefovir or history of resistance to adefovir.
- Hemoglobin \<8 g/dL, or neutrophil count \<1000/uL, or ALT \>5 times ULN, or total bilirubin \>2 mg/dL; or albumin \<25gm/L, or abnormal creatinine level, or abnormal BUN levels.
- History of abortion, or congenital malformation, or child infected with HBV in a prior pregnancy.
- Biological father of the child (current pregnancy) has CHB.
- Significant renal, cardiovascular, pulmonary, or neurological disease that may impact the subject's participation in the study as per the opinion of the investigator.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Pingdingshan Hospital of Chongqing Public Health Medical Treatment Center
Shapingba, Chongqing Municipality, China
First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
The Seventh Affiliated Hospital, Sun Yat-sen University
Shenzhen, Guangdong, China
Hainan General Hospital
Haikou, Hainan, China
The Third Hospital of Qinhuangdao
Qinhuangdao, Hebei, China
The Fourth Hospital of Harbin Medical University
Harbin, Heilonjiang, China
Xiangya Hospital, Central South University
Changsha, Hunan, China
Ganzhou Fifth People's Hospital
Ganzhou, Jiangxi, China
Shengjing Hospital of China Medical University
Shenyang, Liaoning, China
Shanghai Public Health Clinical Center, Fudan University
Zhujing, Shanghai Municipality, 201508, China
Yuyao People's Hospital of Zhejiang Province
Yuyao, Zhejiang, China
Related Publications (5)
Xu WM, Cui YT, Wang L, Yang H, Liang ZQ, Li XM, Zhang SL, Qiao FY, Campbell F, Chang CN, Gardner S, Atkins M. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat. 2009 Feb;16(2):94-103. doi: 10.1111/j.1365-2893.2008.01056.x. Epub 2008 Oct 8.
PMID: 19175878BACKGROUNDZou H, Chen Y, Duan Z, Zhang H. Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers. PLoS One. 2011;6(10):e26748. doi: 10.1371/journal.pone.0026748. Epub 2011 Oct 28.
PMID: 22053208BACKGROUNDPan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H; China Study Group for the Mother-to-Child Transmission of Hepatitis B. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016 Jun 16;374(24):2324-34. doi: 10.1056/NEJMoa1508660.
PMID: 27305192BACKGROUNDJourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B. N Engl J Med. 2018 Mar 8;378(10):911-923. doi: 10.1056/NEJMoa1708131.
PMID: 29514030BACKGROUNDWiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust. 2009 May 4;190(9):489-92. doi: 10.5694/j.1326-5377.2009.tb02524.x.
PMID: 19413519BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Calvin Pan, MD
Beijing Ditan Hospital, Capital Medical University; NYU Langone Health, NY, USA
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 6, 2019
First Posted
December 26, 2019
Study Start
January 27, 2020
Primary Completion
September 30, 2021
Study Completion
September 30, 2021
Last Updated
December 29, 2020
Record last verified: 2020-12