Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen

BMC Infectious Diseases

Study Protocol

Linda Harrison¹  Lei Hua¹  Camlin Tierney¹  Trudy V. Murphy²  Woottichai Khamduang³  Wasna Sirirungsi³  Jullapong Achalapong⁴  Nantasak Chotivanich⁵  Chureeratana Bowonwatanuwong⁵  Suchat Hongsiriwon⁶  Thanyawee Puthanakit⁷  Stanislas Pol⁸  Satawat Thongsawat⁹  Patrinee Traisathit^1,10  George K. Siberry^1,11  Nicolas Salvadori^1,12  Luc Decker^1,12  Gonzague Jourdain^1,13  Nicole Ngo-Giang-Huong^1,13  Tim R. Cressey^1,14  Raymond T. Chung^1,15  Virat Klinbuayaem^1,16  Diane Heather Watts^1,17 

[1] Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, 677 Huntington Ave, 02115, Boston, MA, USA;Centers for Disease Control and Prevention, DHHS/CDC//NCHHSTP/DVH/Vaccine Unit Bldg Corporate SQ 12, Room 3111, 30329-1902, Atlanta, GA, USA;Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., 50200, Sripoom, Chiang Mai, Thailand;Chiangrai Prachanukroh Hospital, Obstetrics & Gynecology Department, 1039 Sathan Phayaban Rd., 57000, Muang, Chiang Rai, Thailand;Chonburi Hospital, 69 M.2, Sukhumvit Rd., Ban-suan, 20000, Muang, Chonburi, Thailand;Chonburi Hospital, Pediatrics Department, 69 M.2, Sukhumvit Rd., Ban-suan, 20000, Muang, Chonburi, Thailand;Chulalongkorn University, Faculty of Medicine, 1873 Rama 4 Road, 10330, Pathumwan, Bangkok, Thailand;Department of Hepato-Gastroenterology, Cochin University Hospital, 27 rue du Faubourg Saint-Jacques, 75679, Paris, Cedex 14, France;Department of Internal Medicine, Chiang Mai University, Faculty of Medicine, 50200, Muang, Chiang Mai, Thailand;Department of Statistics, Chiang Mai University, Faculty of Science, 239 Huaykaew Rd., Suthep, 50200, Muang, Chiang Mai, Thailand;Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, 20892, Bethesda, MD, USA;Institut de recherche pour le développement (IRD, France), UMI 174 – PHPT, 187/10, Changklan Rd., Changklan, 50100, Muang, Chiang Mai, Thailand;Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., 50200, Sripoom, Chiang Mai, Thailand;Institut de recherche pour le développement (IRD, France), UMI 174 – PHPT, 187/10, Changklan Rd., Changklan, 50100, Muang, Chiang Mai, Thailand;Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., 50200, Sripoom, Chiang Mai, Thailand;Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, 02115, Boston, MA, USA;Institut de recherche pour le développement (IRD, France), UMI 174 – PHPT, 187/10, Changklan Rd., Changklan, 50100, Muang, Chiang Mai, Thailand;Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., 50200, Sripoom, Chiang Mai, Thailand;Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, 02115, Boston, MA, USA;Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK;Massachusetts General Hospital, Gastrointestinal Unit, WRN 1007C, GI Unit, 55 Fruit St, 02114, Boston, MA, USA;Sanpatong Hospital, Medical Department, 149 M.15 Yuhwa, 50120, Sanpatong, Chiang Mai, Thailand;US Department of State, Office of the Global AIDS Coordinator, SA-22, 2201 C Street NW, 20522-2210, Washington, DC, USA;

关键词: Hepatitis B;    Hepatitis B surface antigen;    Hepatitis B e antigen;    Pregnancy;    Mother-to-child transmission;    Thailand;   

DOI  :  10.1186/s12879-016-1734-5

 received in 2016-06-13, accepted in 2016-07-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundChronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV.MethodsThe study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1:1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks’ gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age ≥18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance >50 mL/min, and no history of anti-HBV antiviral treatment.The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a ≥9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT >300 IU/L, defined as a “flare”) following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age.DiscussionThe results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines.Trial registrationClinicalTrials.gov Identifier NCT01745822.

【 授权许可】

CC BY   
© The Author(s). 2016