Long-term Effectiveness of a Recombinant Hepatitis E Vaccine

Long-term Effectiveness of a Recombinant Hepatitis E Vaccine: a Test-negative Design Study

This test-negative study is designed to evaluate the long-term effectiveness of hepatitis E vaccine (Hecolin®) and to explore the prevalence of rat hepatitis E in Dongtai City.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis E
• Intervention / Treatment: Diagnostic test: serology and virology detection of hepatitis E virus

Detailed Description

In this negative test study, residual clinical serum will be collected from 13 hospitals in Dongtai, if it was from patients born between 1941-1991 from 11 towns in Dongtai, who tested positive for ALT levels higher than 2.5 times the upper limit of normal (ULN). Detection of HEV IgM, IgG, antigen, RNA will be performed to diagnose hepatitis E (HE) in each individual. In addition, HE vaccination history will be collect. All the information above will be used to evaluate the long-term effectiveness of HE vaccine. Based on the study design, virological and serological detection (IgM, IgG, antigen, and RNA) of hepatitis E virus species C (HEV-C) will be performed to analyze the prevalence of rat hepatitis E infection in Dongtai.

• Study Type: Observational
• Enrollment (Estimated): 2900

Contacts and Locations

• Study Contact: Name: Zhang Jun, PhD; Phone Number: 0592-2184110; Email: zhangj@xmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Dongtai, Jiangsu, China, 224200
      • Recruiting
      • Dongtai Center for Disease Control and Prevention
      • Contact: Yang Changlin; Phone Number: 0515-85212669; Email: 759106863@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients from the designated township who met the criteria of "ALT ≥ 2.5 ULN" and born between 1941 and 1991 will be enrolled in the study.

Description

Inclusion Criteria:

1. From 11 townships（Anfeng、Fuan、Tangyang、Hougang、Liangduo、Qingdong、Shiyan、Shenzao、Wulie、Xuhe、Xinjie）
2. ALT ≥ 2.5 ULN
3. Born between 1941 and 1991

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HE group; Subjects who has been diagnosed as HE.	Diagnostic test: serology and virology detection of hepatitis E virus; Serum will be tested for HEV serology and virology, including HEV-IgM, HEV-IgG, HEV-antigen, and HEV-RNA for HEV species A (HEV-A) and HEV species C (HEV-C)，and further HEV genotyping for those positive for HEV-RNA.
Control group; Subjects who didn't meet the diagnosis criteria of HE.	Diagnostic test: serology and virology detection of hepatitis E virus; Serum will be tested for HEV serology and virology, including HEV-IgM, HEV-IgG, HEV-antigen, and HEV-RNA for HEV species A (HEV-A) and HEV species C (HEV-C)，and further HEV genotyping for those positive for HEV-RNA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of hepatitis E infection	In patients with ALT > 2.5 ULN, HEV infection is diagnosed as positive when two of the following indicators are positive: (1) HEV-IgM; (2) Seroconversion or four-fold increase of HEV-IgG；(3) HEV-RNA; (4) HEV-antigen.	Two months after sampling

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of rat hepatitis E infection	In patients with ALT > 2.5 ULN, rat hepatitis E infection is diagnosed as positive when two of the following virologic or serological tests are positive: (1) IgM anti-HEV-C-; (2) IgG anti-HEV-C- seroconversion or four-fold increase；(3) HEV-C-RNA; (4) HEV-C-antigen.	Two months after sampling

Collaborators and Investigators

• Sponsor: Xiamen University
• Collaborators: Dongtai People's Hospital; Dongtai Center for Disease Control and Prevention; Dongtai Hospital of Traditional Chinese Medicine
• Investigators: Study Director: Zhang Jun, M.D., National Institute of Diagnostics and Vaccine Development in infectious disease, Xiamen University

Publications and helpful links

General Publications

• Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.
• Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, Guo M, Liu XH, Li JX, Yang CL, Tang Q, Jiang RJ, Pan HR, Li YM, Shih JW, Ng MH, Zhu FC, Xia NS. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5;372(10):914-22. doi: 10.1056/NEJMoa1406011. Erratum In: N Engl J Med. 2015 Apr 9;372(15):1478.

Study record dates

Study Major Dates

• Study Start (Estimated): August 12, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 28, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 12, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Vaccine; Effectiveness; Hepatitis E; Test-Negative Design; Rat hepatitis E virus infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis E
• Other Study ID Numbers: PRO-HE-004-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing requires investigator consent

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No