title: 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.
abstract: Chronic 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.
  
  
  
  The 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.
  
  
  
  The 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.
  
  
  
  ClinicalTrials.gov Identifier NCT01745822 .
authors: Institut de recherche pour le développement (IRD, France), UMI 174 - PHPT, 187/10, Changklan Rd., Changklan, Muang, Chiang Mai, 50100, Thailand. gonzague.jourdain@ird.fr.|Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand. gonzague.jourdain@ird.fr.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA. gonzague.jourdain@ird.fr.
authors: Gonzague
authors: 0000-0002-3365-7020
authors: G
authors: Jourdain
authors: Institut de recherche pour le développement (IRD, France), UMI 174 - PHPT, 187/10, Changklan Rd., Changklan, Muang, Chiang Mai, 50100, Thailand.|Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
authors: Nicole
authors: N
authors: Ngo-Giang-Huong
authors: Institut de recherche pour le développement (IRD, France), UMI 174 - PHPT, 187/10, Changklan Rd., Changklan, Muang, Chiang Mai, 50100, Thailand.|Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.|Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors: Tim R
authors: TR
authors: Cressey
authors: Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
authors: Lei
authors: L
authors: Hua
authors: Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
authors: Linda
authors: L
authors: Harrison
authors: Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
authors: Camlin
authors: C
authors: Tierney
authors: Institut de recherche pour le développement (IRD, France), UMI 174 - PHPT, 187/10, Changklan Rd., Changklan, Muang, Chiang Mai, 50100, Thailand.|Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.
authors: Nicolas
authors: N
authors: Salvadori
authors: Institut de recherche pour le développement (IRD, France), UMI 174 - PHPT, 187/10, Changklan Rd., Changklan, Muang, Chiang Mai, 50100, Thailand.|Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.
authors: Luc
authors: L
authors: Decker
authors: Department of Statistics, Chiang Mai University, Faculty of Science, 239 Huaykaew Rd., Suthep, Muang, Chiang Mai, 50200, Thailand.
authors: Patrinee
authors: P
authors: Traisathit
authors: Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.
authors: Wasna
authors: W
authors: Sirirungsi
authors: Chiang Mai University, Faculty of Associated Medical Sciences, 110 Intawaroroj Rd., Sripoom, Chiang Mai, 50200, Thailand.
authors: Woottichai
authors: W
authors: Khamduang
authors: Chonburi Hospital, 69 M.2, Sukhumvit Rd., Ban-suan, Muang, Chonburi, 20000, Thailand.
authors: Chureeratana
authors: C
authors: Bowonwatanuwong
authors: Chulalongkorn University, Faculty of Medicine, 1873 Rama 4 Road, Pathumwan, Bangkok, 10330, Thailand.
authors: Thanyawee
authors: T
authors: Puthanakit
authors: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Blvd, Bethesda, MD, 20892, USA.
authors: George K
authors: GK
authors: Siberry
authors: US Department of State, Office of the Global AIDS Coordinator, SA-22, 2201 C Street NW, Washington, DC, 20522-2210, USA.
authors: Diane Heather
authors: DH
authors: Watts
authors: Centers for Disease Control and Prevention, DHHS/CDC//NCHHSTP/DVH/Vaccine Unit Bldg Corporate SQ 12, Room 3111, Atlanta, GA, 30329-1902, USA.
authors: Trudy V
authors: TV
authors: Murphy
authors: Chiangrai Prachanukroh Hospital, Obstetrics & Gynecology Department, 1039 Sathan Phayaban Rd., Muang, Chiang Rai, 57000, Thailand.
authors: Jullapong
authors: J
authors: Achalapong
authors: Chonburi Hospital, Pediatrics Department, 69 M.2, Sukhumvit Rd., Ban-suan, Muang, Chonburi, 20000, Thailand.
authors: Suchat
authors: S
authors: Hongsiriwon
authors: Sanpatong Hospital, Medical Department, 149 M.15 Yuhwa, Sanpatong, Chiang Mai, 50120, Thailand.
authors: Virat
authors: V
authors: Klinbuayaem
authors: Department of Internal Medicine, Chiang Mai University, Faculty of Medicine, Muang, Chiang Mai, 50200, Thailand.
authors: Satawat
authors: S
authors: Thongsawat
authors: Massachusetts General Hospital, Gastrointestinal Unit, WRN 1007C, GI Unit, 55 Fruit St, Boston, MA, 02114, USA.
authors: Raymond T
authors: RT
authors: Chung
authors: Department of Hepato-Gastroenterology, Cochin University Hospital, 27 rue du Faubourg Saint-Jacques, 75679, Paris, Cedex 14, France.
authors: Stanislas
authors: S
authors: Pol
authors: Chonburi Hospital, 69 M.2, Sukhumvit Rd., Ban-suan, Muang, Chonburi, 20000, Thailand.
authors: Nantasak
authors: N
authors: Chotivanich
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019072:Antibiotic Prophylaxis / Q000379:methods; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D006509:Hepatitis B / Q000517:prevention & control / Q000635:transmission*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D009035:Mothers; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D000068698:Tenofovir / Q000627:therapeutic use*; D013785:Thailand; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D007136:Immunoglobulins; D000068698:Tenofovir; D000410:Alanine Transaminase; C045213:hepatitis B hyperimmune globulin
keywords: Hepatitis B; Hepatitis B e antigen; Hepatitis B surface antigen; Mother-to-child transmission; Pregnancy; Thailand