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Tenofovir Disoproxil Fumarate in Combination of Hepatitis B Vaccine for Preventing Hepatitis B Vertical Transmission

NCT ID: NCT03476083

Last Updated: 2019-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

280 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-10

Study Completion Date

2024-05-31

Brief Summary

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Immunoprophylaxis with two hepatitis B vaccinations following the hepatitis B immune globulin (HBIg) and hepatitis B vaccine at birth is largely effective in protecting infants from hepatitis B virus (HBV) infection. However, hepatitis B infection due to immunoprophylaxis failure often occurs in approximately 10% of infants who are born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA \> 200,000 IU/mL is the major independent risk for mother-to-child transmission (MTCT). A recent randomized controlled trial has shown that Tenofovir Disoproxil Fumarate (TDF) use during the third trimester of pregnancy could safely reduce the rate of MTCT with few adverse effects when combined with the administration of the standard immunoprophylaxis to the infants. However, HBIg is expensive and not available in many developing countries, resulting approximately 30% of infant infection when they received only HBV vaccination. The present study aims to investigate if highly viremic mothers who are treated with TDF from the second trimester to delivery in combination of infant's standard series of HBV vaccinations (omission of HBIg) have a comparable MTCT rates, when compared to those of mothers who receive TDF at the third trimester in combination of infant's standard HBV vaccinations and a birth dose of HBIg.

Detailed Description

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This is a multicenter, prospective, randomized, open-label and parallel two arm study starting from week 14-16 of pregnancy to post-partum week 28. The enrollment from approximately 7 centers will be in blocks for sample balance. By using the randomized table, 280 HBeAg-positive pregnant women with chronic hepatitis B (CHB) will be randomized in a 1:1 ratio in to two arms. Group assignments will be also stratified by the maternal HBV DNA levels \>9 log10 versus ≤ 9 log10 IU/mL.

Group A: This is the experimental group. Participating mothers will receive TDF (oral 300 mg tablet daily) starting at gestational weeks 14-16 and continue until delivery. The mothers will be followed together with their infants until postpartum week 28. Infants will receive hepatitis B vaccine at birth (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24. HBIg will be omitted for the infants in this group. However, the birth dose of HBIg will be provided to infants born to mothers who have poor control of maternal viremia (i.e. the levels of HBV DNA \>200,000 IU/mL before delivery). Group B: This is the comparative group. Participating mothers will receive TDF (oral 300 mg tablet daily) starting at gestational weeks 28 and continue until delivery. Patients in group B will have similar follow-up schedules as those in the experimental group. 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.

Conditions

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Hepatitis B Infection Congenital Malformation Birth Defect Viremia Chronic Infection

Keywords

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Mother to Child Transmission Hepatitis B Infection Congenital Defects or Malformation Hepatitis B Vaccine Hepatitis B Immunoglobulin Pregnancy Antiviral Treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group A

This is the experimental group. Participating mothers will receive Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily, starting at gestational weeks 14-16 and continue until delivery. The mothers will be followed together with their infants until postpartum week 28. Infants will receive hepatitis B vaccine at birth and additional hepatitis B (HBV) vaccine at the age of week 4 and week 24. HBIg will be omitted for the infants in this group.

Group Type EXPERIMENTAL

Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.

Intervention Type DRUG

All mothers will receive TDF therapy. However, group A will initiate TDF at the gestational week of 14-16, while group B will initiate TDF at the gestational week of 28. All infants will receive a series of three hepatitis B vaccines (at birth, age of weeks 4 and 24). In addition, the infants in the group B will receive HBIg injection at birth.

Group B

This is the comparative group. Participating mothers will receive Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily, starting at gestational weeks 28 and continue until delivery. Patients in group B will have similar follow-up schedules as those in the experimental group. Infants will receive hepatitis B vaccine plus HBIg at birth and additional hepatitis B vaccine at the age of week 4 and week 24.

Group Type ACTIVE_COMPARATOR

Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.

Intervention Type DRUG

All mothers will receive TDF therapy. However, group A will initiate TDF at the gestational week of 14-16, while group B will initiate TDF at the gestational week of 28. All infants will receive a series of three hepatitis B vaccines (at birth, age of weeks 4 and 24). In addition, the infants in the group B will receive HBIg injection at birth.

Interventions

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Tenofovir Disoproxil Fumarate (TDF) 300 mg oral daily.

All mothers will receive TDF therapy. However, group A will initiate TDF at the gestational week of 14-16, while group B will initiate TDF at the gestational week of 28. All infants will receive a series of three hepatitis B vaccines (at birth, age of weeks 4 and 24). In addition, the infants in the group B will receive HBIg injection at birth.

Intervention Type DRUG

Other Intervention Names

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HBIg 200 IU im for infants in the group B HBV vaccine 10 ug im for all infants

Eligibility Criteria

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Inclusion Criteria

* HBeAg-positive CHB mothers
* Age of 20-35 years old
* Serum HBV DNA levels \> 200,000 IU/mL
* Gestational age between 12-14 weeks.
* Both mother and father of the child have the ability to understand and are willing to consent to the study.

Exclusion Criteria

* Co-infection with (HIV)-1, or hepatitis A, C, D, E or sexual transmitted diseases (STD)
* History of abortion or congenital malformation in a prior pregnancy
* Treatment experience (except when antivirals were used for MTCT prevention in a previous pregnancy and discontinued \>6 months prior to the current pregnancy)
* History of renal dysfunction; evidence of liver cancer or decompensation
* Estimated creatinine clearance (CLCr) \<100 mL/min (using the Cockcroft-Gault method based on serum creatinine and ideal body weight)
* Hypo-phosphoremia; hemoglobin \<8 g/dL; neutrophil count \<1,000//μL; alanine aminotransferase \>5 times upper limit of the normal; total bilirubin \>2 mg/dL; albumin \<25gm/L;
* Clinical signs of threatened miscarriage
* Ultrasonographic evidence of fetal deformity
* Concurrent treatment with nephrotoxic drugs, steroids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or immune modulators;
* Recipient of solid organ or bone marrow transplant
* Significant renal, cardiovascular, pulmonary, neurological disease or other health conditions in the opinion of the investigator
* Fetus's biological father had CHB infection
Minimum Eligible Age

20 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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New Discovery LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Calvin Q Pan, MD

Role: STUDY_CHAIR

Leading Principle Investigator, NYU Langone Health, NYU School of Medicine, NY

Erhei Dai, MD

Role: STUDY_DIRECTOR

The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, China

Locations

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Beijing Youan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status RECRUITING

Southwest Hospital

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Guangzhou Women and Children's Medical Center, Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, China

Site Status RECRUITING

Shijiazhuang Maternal and Child Health Care Hospital

Shijiazhuang, Hebei, China

Site Status RECRUITING

Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status RECRUITING

The Third People's Hospital of Shenzhen

Shenzhen, Shenzhen, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xiuli Chen, MD

Role: CONTACT

Phone: +86-13363887189

Email: [email protected]

Erhei Dai, MD

Role: CONTACT

Phone: +86-13323119296

Email: [email protected]

Facility Contacts

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Hua Zhang, MD

Role: primary

Huaibin Zou, MD

Role: backup

Jie Wang, MD

Role: primary

Shilian Li, MD

Role: backup

Jinjuan Wu, MD

Role: primary

Thomas Q Zheng, MD

Role: backup

Hongxia Tian, MD

Role: primary

Suwen Li, MD

Role: backup

Cuili Yang, MD

Role: primary

Jing Liu, MD

Role: backup

Taotao Yan, MD

Role: primary

Yingren Zhao, MD

Role: backup

Liuqing Yang, MD

Role: primary

Yanjie Li, MD

Role: backup

References

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Ott JJ, Stevens GA, Wiersma ST. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen (HBeAg) prevalence estimates for all world regions. BMC Infect Dis. 2012 Jun 9;12:131. doi: 10.1186/1471-2334-12-131.

Reference Type BACKGROUND
PMID: 22682147 (View on PubMed)

Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, Tong MJ. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol. 2012 May;10(5):452-9. doi: 10.1016/j.cgh.2011.10.041. Epub 2011 Nov 9.

Reference Type BACKGROUND
PMID: 22079509 (View on PubMed)

Pande C, Sarin SK, Patra S, Kumar A, Mishra S, Srivastava S, Bhutia K, Gupta E, Mukhopadhyay CK, Dutta AK, Trivedi SS. Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial. J Viral Hepat. 2013 Nov;20(11):801-10. doi: 10.1111/jvh.12102. Epub 2013 Apr 23.

Reference Type BACKGROUND
PMID: 24168259 (View on PubMed)

Lee LY, Aw MM, Saw S, Rauff M, Tong PY, Lee GH. Limited benefit of hepatitis B immunoglobulin prophylaxis in children of hepatitis B e antigen-negative mothers. Singapore Med J. 2016 Oct;57(10):566-569. doi: 10.11622/smedj.2015194. Epub 2015 Dec 29.

Reference Type BACKGROUND
PMID: 26778725 (View on PubMed)

Machaira M, Papaevangelou V, Vouloumanou EK, Tansarli GS, Falagas ME. Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis. J Antimicrob Chemother. 2015 Feb;70(2):396-404. doi: 10.1093/jac/dku404. Epub 2014 Oct 31.

Reference Type BACKGROUND
PMID: 25362571 (View on PubMed)

Pan 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.

Reference Type BACKGROUND
PMID: 27305192 (View on PubMed)

Pan, C. Q.; Chang, T. T.; Bae, S. H.; Brunetto, M.; Coffin, C.; Lau, A.; Mo, S.; Flaherty, J. F.; Gaggar, A.; Subramanian, G. M.; Nguyen, M. H.; Gurel, S.; Thompson, A.; Gane, E. J. Viral kinetics in women of child bearing potential with chronic hepatitis B virus following treatment with tenofovir alafenamide or tenofovir disoproxil fumarate. J Hepatol. 2017;66 S258-S259.

Reference Type BACKGROUND

Pan CQ, Dai E, Mo Z, Zhang H, Zheng TQ, Wang Y, Liu Y, Chen T, Li S, Yang C, Wu J, Chen X, Zou H, Mei S, Zhu L. Tenofovir and Hepatitis B Virus Transmission During Pregnancy: A Randomized Clinical Trial. JAMA. 2025 Feb 4;333(5):390-399. doi: 10.1001/jama.2024.22952.

Reference Type DERIVED
PMID: 39540799 (View on PubMed)

Other Identifiers

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(2018) 462 No: HGRSL20180412

Identifier Type: OTHER

Identifier Source: secondary_id

US-G10-P616

Identifier Type: -

Identifier Source: org_study_id