Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03343431
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : August 19, 2019
Sponsor:
Collaborators:
Chiang Mai University
Ministry of Health, Thailand
Ministry of Health, Lao PDR
Information provided by (Responsible Party):
GONZAGUE JOURDAIN, Institut de Recherche pour le Developpement

Tracking Information
First Submitted Date  ICMJE November 6, 2017
First Posted Date  ICMJE November 17, 2017
Last Update Posted Date August 19, 2019
Actual Study Start Date  ICMJE August 2, 2018
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 11, 2017)
Infant hepatitis B infection status [ Time Frame: Six months of age ]
HBsAg positive confirmed by PCR detection of HBV DNA.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03343431 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2017)
  • Maternal HBV DNA changes [ Time Frame: From enrollment until end of study treatment scheduled 2 months after delivery ]
    Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels
  • Infant levels of anti-HBs antibodies [ Time Frame: At 1, 2, 4, 6, and 12 months of age ]
    Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth
  • HBV infection status in all infants regardless of maternal response to study treatment [ Time Frame: At 6 months of age ]
    HBsAg positive confirmed by PCR detection of HBV DNA in all infants, i.e. including those born to women with unsatisfactory virological response to study treatment
  • Serious adverse events [ Time Frame: From enrollment until 12 months postpartum ]
    Occurrence of maternal serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment
  • Serious adverse events [ Time Frame: From birth until 12 months of age ]
    Occurrence of infant serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment
  • Preterm live births [ Time Frame: Delivery ]
    Proportion of neonates born alive before 37 weeks of pregnancy
  • Low birth weight [ Time Frame: Delivery ]
    Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age
  • Active or previous transient infection in children [ Time Frame: At 18 months of age ]
    Detection of anti-HBc antibodies among all infants
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection
Official Title  ICMJE A Maternal Short Course of Tenofovir Disoproxil Fumarate and Infant Vaccine to Prevent Mother-to-child Transmission of Hepatitis B Virus
Brief Summary Most new hepatitis B virus (HBV) infections are acquired perinatally. In this study, pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate during the last trimester of pregnancy and for two months following delivery. Their infants will receive hepatitis B (HB) immunization, starting with a first dose soon after birth. We hypothesize that the risk of mother-to-child transmission of HBV will be lower than 2%. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.
Detailed Description

This is a prospective multi-center, multi-country (Thailand and Lao PDR), open-label, single arm clinical trial in HBsAg and HBeAg positive pregnant women (from 28 weeks until one year postpartum) and their infants (until 18 months of age). Pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate 300 mg once daily from 28 weeks of pregnancy until two months postpartum. Their infants will receive hepatitis B (HB) immunization, starting with the first dose soon after birth.

The study aims to show that substituting maternal antiviral treatment for infant HBIg can be favorably considered in settings where HBIg plus vaccine has been used as well as in settings where only vaccine is used. A significant improvement over the standard HBIg + vaccine strategy would be that adding an antiviral strategy results in less than 2% transmission. A total of 499 women and their infants will be enrolled in public hospitals in Thailand and Lao PDR.

The study will be monitored by a Data and Safety Monitoring Board (DSMB) at least annually.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
All participants receive the intervention
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Hepatitis B
  • Pregnancy
Intervention  ICMJE Drug: Anti-HBV antiviral prophylaxis
Tenofovir disoproxil fumarate (TDF), one 300 mg tablet once a day from 28 weeks' gestation through two months postpartum
Other Name: tenofovir disoproxil fumarate
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 11, 2017)
499
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2023
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pregnancy
  • Age ≥18 years
  • Negative HIV antibody test during current pregnancy
  • Positive HBsAg test during current pregnancy
  • Positive HBeAg using a rapid test during current pregnancy
  • Absence of clinical symptoms of liver disease
  • Gestational age of 28 weeks (+/- 7 days) based on the obstetrician judgment guided by the review of the date of last menstruation period.
  • Willing and able to provide written informed consent
  • Agreeing to bring her infants(s) at the planned study visits at one of the study site until the last visit (18 months after birth) and to inform the site investigators if plans to move to another place and not be able to return to the clinic
  • Understand the need for adequate infant immunization for her infant(s) and accept that blood draws will be performed to determine the infant HBV infection status

Exclusion Criteria:

  • Receipt of anti-HBV antivirals at any time during the last 9 months
  • Known liver cirrhosis or evidence of hepatocellular carcinoma
  • Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula
  • Confirmed dipstick proteinuria >1+ (>30 mg/dL) or normoglycemic glycosuria
  • Evidence of pre-existing fetal anomalies incompatible with life
  • Any concomitant condition or treatment that, in the view of the clinical site investigator, would contraindicate participation or compromise adherence to treatment and satisfactory follow up in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Pregnant women
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gonzague Jourdain, MD, PhD +66818830065 Gonzague.Jourdain@ird.fr
Contact: Nicole Ngo-Giang-Huong, PharmD, PhD +66898511178 Nicole.Ngo-Giang-Huong@phpt.org
Listed Location Countries  ICMJE Lao People's Democratic Republic,   Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03343431
Other Study ID Numbers  ICMJE iTAP-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

We are willing to share our data with other investigators, for example for meta-analysis, in order to answer important research questions requiring large datasets, after completion of the original research plan including substudies. Data-sharing agreements will include: an approval of the research plan by appropriate ethics committees, a commitment to using data for research purposes only and to securing the data or/and the samples using appropriate methods. We will consult as needed with the funding agency the practical aspects of data sharing.

Data used for publications will be released in a timely manner. De-identified study data could be accessible through a website that allows querying such as the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub or DASH (dash.nichd.nih.gov/).

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: At the same time as related publications
Access Criteria: See Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub or DASH
URL: https://dash.nichd.nih.gov
Responsible Party GONZAGUE JOURDAIN, Institut de Recherche pour le Developpement
Study Sponsor  ICMJE Institut de Recherche pour le Developpement
Collaborators  ICMJE
  • Chiang Mai University
  • Ministry of Health, Thailand
  • Ministry of Health, Lao PDR
Investigators  ICMJE
Principal Investigator: Gonzague Jourdain, MD, PhD Institut de Recherche pour l e Développement
PRS Account Institut de Recherche pour le Developpement
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP