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
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, Ch...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2020-01-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/10/1/e033702.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846141593513361408 |
|---|---|
| author | Anisur Rahman K Zaman Susanne Dudman Kathrine Stene-Johansen Firdausi Qadri Md Yunus Synne Sandbu Emily S Gurley Joakim Overbo Cathinka Halle Julin Jennifer Lynn Dembinski Quamrun Nahar Taufiqur R Bhuiyan Mustafizur Rahman Warda Haque Jahangir Khan Asma Aziz Mahbuba Khanam Peter Kim Streatfield John D Clemens |
| author_facet | Anisur Rahman K Zaman Susanne Dudman Kathrine Stene-Johansen Firdausi Qadri Md Yunus Synne Sandbu Emily S Gurley Joakim Overbo Cathinka Halle Julin Jennifer Lynn Dembinski Quamrun Nahar Taufiqur R Bhuiyan Mustafizur Rahman Warda Haque Jahangir Khan Asma Aziz Mahbuba Khanam Peter Kim Streatfield John D Clemens |
| author_sort | Anisur Rahman |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6d3d1aa60ebb42578636ac1e22a61ad3 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-6d3d1aa60ebb42578636ac1e22a61ad32024-12-04T05:40:09ZengBMJ Publishing GroupBMJ Open2044-60552020-01-0110110.1136/bmjopen-2019-033702HEV 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 BangladeshAnisur Rahman0K Zaman1Susanne Dudman2Kathrine Stene-Johansen3Firdausi Qadri4Md Yunus5Synne Sandbu6Emily S Gurley7Joakim Overbo8Cathinka Halle Julin9Jennifer Lynn Dembinski10Quamrun Nahar11Taufiqur R Bhuiyan12Mustafizur Rahman13Warda Haque14Jahangir Khan15Asma Aziz16Mahbuba Khanam17Peter Kim Streatfield18John D Clemens19Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Dhaka District, BangladeshInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, BangladeshInstitute of Clinical Medicine, University of Oslo, Oslo, NorwayDivision of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, BangladeshInternational Centre for Diarhoeal Disease Resaerch, Dhaka, BangladeshDivision of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayInternational Centre for Diarhoeal Disease Resaerch, Dhaka, BangladeshDivision of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayDivision of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayDivision of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayMaternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, BangladeshInternational Centre for Diarhoeal Disease Resaerch, Dhaka, BangladeshInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, BangladeshInternational Centre for Diarhoeal Disease Resaerch, Dhaka, BangladeshSchool of Public Health and Community Medicine, University of Gothenburg, Goteborg, Västra Götaland, Sweden3Barking Havering and Redbridge University Hospitals NHS Trust, Obstetrics and Gynaecology, Romford, United KingdomInternational Centre for Diarhoeal Disease Resaerch, Dhaka, BangladeshHealth Systems and Population Studies Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, BangladeshInfectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, BangladeshIntroduction 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.https://bmjopen.bmj.com/content/10/1/e033702.full |
| spellingShingle | Anisur Rahman K Zaman Susanne Dudman Kathrine Stene-Johansen Firdausi Qadri Md Yunus Synne Sandbu Emily S Gurley Joakim Overbo Cathinka Halle Julin Jennifer Lynn Dembinski Quamrun Nahar Taufiqur R Bhuiyan Mustafizur Rahman Warda Haque Jahangir Khan Asma Aziz Mahbuba Khanam Peter Kim Streatfield John D Clemens 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 BMJ Open |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/10/1/e033702.full |
| work_keys_str_mv | AT anisurrahman hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT kzaman hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT susannedudman hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT kathrinestenejohansen hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT firdausiqadri hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT mdyunus hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT synnesandbu hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT emilysgurley hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT joakimoverbo hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT cathinkahallejulin hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT jenniferlynndembinski hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT quamrunnahar hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT taufiqurrbhuiyan hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT mustafizurrahman hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT wardahaque hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT jahangirkhan hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT asmaaziz hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT mahbubakhanam hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT peterkimstreatfield hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh AT johndclemens hevstudyprotocoldesignofaclusterrandomisedblindedtrialtoassessthesafetyimmunogenicityandeffectivenessofthehepatitisevaccinehev239hecolininwomenofchildbearingageinruralbangladesh |