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Infectious diseases
Protocol
HEV study protocol : design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh
  1. K Zaman1,
  2. Susanne Dudman2,3,
  3. Kathrine Stene-Johansen3,
  4. Firdausi Qadri1,
  5. Md Yunus1,
  6. Synne Sandbu3,
  7. Emily S Gurley1,4,
  8. Joakim Overbo3,
  9. Cathinka Halle Julin3,
  10. Jennifer Lynn Dembinski3,
  11. Quamrun Nahar1,
  12. Anisur Rahman1,
  13. Taufiqur R Bhuiyan1,
  14. Mustafizur Rahman1,
  15. Warda Haque1,
  16. Jahangir Khan1,5,
  17. Asma Aziz1,
  18. Mahbuba Khanam1,
  19. Peter Kim Streatfield1,
  20. John D Clemens1,6
  1. 1International Centre for Diarhoeal Disease Resaerch, Dhaka, Bangladesh
  2. 2Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  3. 3Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
  4. 4Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
  5. 5Health Economics, Liverpool School of Tropical Medicine, Liverpool, UK
  6. 6University of California Los Angeles Jonathan and Karin Fielding School of Public Health, Los Angeles, California, USA
  1. Correspondence to Dr K Zaman; kzaman{at}icddrb.org

Abstract

Introduction Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in the developing world and is a public health problem, in particular among pregnant women, where it may lead to severe or fatal complications. A recombinant HEV vaccine, 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China), is licensed in China, but WHO calls for further studies to evaluate the safety and immunogenicity of this vaccine in vulnerable populations, and to evaluate protection in pregnancy. We are therefore conducting a phase IV trial to assess the effectiveness, safety and immunogenicity of the HEV 239 vaccine when given in women of childbearing age in rural Bangladesh, where HEV infection is endemic.

Methods and analysis Enrolment of a target of approximately 20 000 non-pregnant women, aged 16–39 years, started on 2 October 2017 in Matlab, Bangladesh. Sixty-seven villages were randomised by village at a 1:1 ratio to receive either the HEV vaccine or the control vaccine (hepatitis B vaccine). A 3-dose vaccination series at 0, 1 and 6 months is ongoing, and women are followed up for 24 months. The primary outcome is confirmed HEV disease among pregnant women. After vaccination, participants are requested to report information about clinical hepatitis symptoms. Participants who become pregnant are visited at their homes every 2 weeks to collect information about pregnancy outcome and to screen for clinical hepatitis. All suspected hepatitis cases undergo laboratory testing for diagnostic evaluation. The incidence of confirmed HEV disease among pregnant and non-pregnant women will be compared between the HEV vaccinated and control groups, safety and immunogenicity of the vaccine will also be evaluated.

Ethics and dissemination The protocol was reviewed and approved by the International Centre for Diarrhoeal Disease Research, Bangladesh Research Review Committee and Ethical Review Committee, and the Directorate General of Drug Administration in Bangladesh, and by the Regional Ethics Committee in Norway. This article is based on the protocol version 2.2 dated 29 June 2017. We will present the results through peer-reviewed publications and at international conferences.

Trial registration number The trial is registered at clinicaltrials.gov with the registry name “Effectiveness Trial to Evaluate Protection of Pregnant Women by Hepatitis E Vaccine in Bangladesh” and the identifier NCT02759991.

  • immunology
  • epidemiology
  • hepatobiliary disease
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2019-033702

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    Footnotes

    • Twitter @Asma Aziz

    • Presented at The authors presented a poster of the study at 10th Conference on Global Health and Vaccination (GLOBVAC) Research in Trondheim, Norway in 2017.

    • Contributors JDC, KZ, SD, KS-J, FQ, MY, SS, JO, ESG, JLD, QN, AR, PKS, JK and CHJ contributed to study design. KZ, JDC, AA, MK, SD, KS-J, JO, SS, TRB, MR, WH, JLD and CHJ were involved in trial management. CHJ, KS-J, SD, JDC, KZ, SS, JLD, JO and ESG contributed in manuscript writing and editing. KZ, AA, MK and WH responsible for managing the field teams/logistics of the study. All authors read and approved the final manuscript.

    • Funding The Research Council of Norway supported this study through the GLOBVAC program, project number 248143. Xiamen Innovax Biotech, China, provided the bulk HEV 239 vaccine. SGD is supported by both NIPH and University of Oslo, KSJ and JLD are additionally supported by NIPH, who also provided additional support from statisticians, technical engineers, vaccine experts and access to laboratory facilities and instruments. The design, management, analysis and reporting of the study are entirely independent of the vaccine manufacturers.

    • Competing interests None declared.

    • Patient consent for publication Obtained.

    • Ethics approval This trial is approved by the icddr,b Research Review Committee and Ethical Review Committee, and by the Directorate General of Drug Administration in Bangladesh. Further, it has been approved by the Regional Ethics Committee in Norway.

    • Provenance and peer review Not commissioned; externally peer reviewed.