Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand (iTAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Institut de Recherche pour le Developpement
Sponsor:
Collaborators:
Gilead Sciences
Information provided by (Responsible Party):
Gonzague Jourdain, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT01745822
First received: December 6, 2012
Last updated: February 25, 2014
Last verified: July 2013
  Purpose

Chronic hepatitis B (CHB) infection is complicated by cirrhosis and liver cancer. In Thailand, 7% of adults are chronically infected by Hepatitis B virus (HBV). The risk of perinatal transmission of HBV is about 12% when a mother has a high HBV load in her plasma, even if her infant receive specific immunoglobulin and vaccine.

The hypothesis of this study is that a potent antiviral, tenofovir, can decrease HBV load in HBV infected pregnant women and therefore reduce the risk of perinatal transmission/ Pregnant women participating in this study will receive tenofovir or placebo during the last trimester of pregnancy and two months postpartum. The risk of perinatal transmission will be compared between the two groups.

The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.


Condition Intervention Phase
Hepatitis B Chronic Infection
Pregnancy
Drug: tenofovir disoproxil fumarate
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase 3, Randomized Clinical Trial to Assess the Efficacy and Safety of Tenofovir in Hepatitis B Virus Infected, s and e Antigen Positive, Pregnant Women to Prevent Perinatal Transmission Despite Infant Passive-active HBV Immunization.

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • Infant's Hepatitis B infection status at 6 months of age [ Time Frame: 6 months of age ] [ Designated as safety issue: No ]
    defined as HBsAg positive confirmed by HBV DNA


Secondary Outcome Measures:
  • Adverse events [ Time Frame: from enrollment (28 weeks' gestation) to 12 months postpartum ] [ Designated as safety issue: Yes ]
    Occurrence of maternal and infant adverse events, including maternal and infants Serious Adverse Events (as defined by the International Conference on Harmonization Good Clinical Practice) and NIH Division of AIDS grade 3/4 signs and symptoms, regardless of their relatedness to the study treatment.

  • Flares after study treatment interruption [ Time Frame: Following planned discontinuation of study treatment up to 12 months postpartum ] [ Designated as safety issue: Yes ]
    Flare, or acute exacerbation of hepatitis B, after study treatment interruption is defined as an Alanine Aminotransferase plasma level above 300 IU/mL

  • Infant's HBV infection status [ Time Frame: at or after 6 months through 12 months of age ] [ Designated as safety issue: No ]
    Infants will be considered HBV infected if at any time point at or after 6 months through 12 months of age, a sample tests positive for HBsAg and HBV DNA

  • Infant growth related outcomes, including weight, height and HC Z-scores [ Time Frame: at 6 months and 12 months of age ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 328
Study Start Date: January 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir disoproxil fumarate
tenofovir disoproxil fumarate, 300 mg tablets
Drug: tenofovir disoproxil fumarate
administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Other Names:
  • Viread
  • TDF
  • tenofovir
Placebo Comparator: Placebo
matching placebo (of tenofovir disoproxil fumarate)
Drug: placebo

Detailed Description:

This is a phase III, placebo controlled, double blind, randomized clinical trial to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) given from 28 weeks' gestation until 2 months postpartum to pregnant women with Hepatitis B (HB) virus (HBV) chronic infection and positive for HB s and e antigen to prevent perinatal transmission of HBV to their infants. All infants will receive HBV passive (HB specific immunoglobulin) and active (vaccine) immunization.

Chronic hepatitis B (CHB) infection is complicated by cirrhosis and hepatocellular carcinoma (HCC), the 10th leading cause of death worldwide.

In 2011, about 7% of adults in Thailand were HBsAg carriers. Infant hepatitis B (HB) immunization and HB immune globulin (HBIg) administered at birth effectively prevent most mother-to-child transmission (MTCT) of HBV. However, about 12% of mothers with high load of HBV transmit the virus to their infants, despite active and passive immunization.

Studies have suggested that antiviral treatment at the end of pregnancy and during early postpartum can reduce the risk of transmission to the child. A potential limitation to this approach is the risk of hepatic disease exacerbation following discontinuation of antiviral treatment postpartum, and this risk has not been properly evaluated. No randomized clinical trials have adequately demonstrated the efficacy and safety of maternal antiviral treatment the prevention of mother to child transmission of HBV. This is the reason why this approach is not currently recommended by the Associations for the Study of Liver Diseases.

We hypothesize that a potent antiviral, tenofovir, can decrease HBV viral load in HBV infected pregnant women and therefore reduce the risk of perinatal transmission, before infants are definitely protected by passive-active immunization. We also hypothesize that only moderate exacerbations of liver disease will be observed after discontinuation of a short antiviral course (5 months). While the primary objective of the study is to assess the efficacy of tenofovir versus placebo for the prevention of perinatal transmission, an important secondary objective is the assessment of the risk of postpartum hepatic disease exacerbation.

Within 2 years, 328 women and their infants will be enrolled from public hospitals in Thailand and randomized to receive either tenofovir disoproxil fumarate or matching placebo from 28 weeks of pregnancy until 2 months postpartum. Mothers and infants will be followed until one year postpartum.

The primary endpoint will be the detection of HBsAg and HBV DNA in infants at six months of life. An interim analysis will be conducted when half of the outcomes are available.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pregnancy
  • At least 18 years of age
  • Negative Human Immunodeficiency Virus (HIV) serology
  • Positive HBsAg and hepatitis B e antigen (HBeAg) tests
  • Gestational age of 28 weeks (+ or - 10 days) as determined by obstetrician
  • Alanine Aminotransferase (ALT)≤30 U/L, confirmed ≤60 U/L on a subsequent blood draw
  • Agreeing to bring their infants at the planned study visits at one study site until one year after delivery and to inform the site investigators if they plan to move to another place and not be able to return to the clinic.
  • Understanding the need for adequate infant immunization and agreeing to the blood draws from their infants and the need for close follow up to manage possible exacerbation of hepatitis.

Exclusion Criteria:

  • History of tenofovir treatment at any time, or any other anti-HBV treatment during the current pregnancy
  • Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula
  • Dipstick proteinuria>1+ (>30 mg/dL) or normoglycemic glucosuria confirmed on two separate occasions
  • Positive serology for Hepatitis C infection less than 12 months prior to enrollment
  • 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 satisfactory follow up in the study.
  • Concurrent participation in any other clinical trial without written agreement of the two study teams
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745822

Contacts
Contact: Gonzague Jourdain, MD, PhD +66818830065 Gonzague.Jourdain@ird.fr
Contact: Nicole Ngo-Giang-Huong, PharmD, PhD +66898511178 Nicole.Ngo-Giang-Huong@ird.fr

Locations
Thailand
Mae Chan Hospital Recruiting
Mae Chan, Chiangrai, Thailand, 57110
Contact: Sudanee Buranabanjasatean, MD    +6653771056    sudanee2011@windowslive.com   
Principal Investigator: Sudanee Buranabanjasatean, MD         
Banglamung Hospital Recruiting
Banglamung, Chonburi, Thailand, 20150
Contact: Prateep Kanjanavikai, MD    +6638411551-2    prateep48@hotmail.com   
Contact: Siriluk Phanomcheong, MD    +6638411551-2    siriluk_lukk@yahoo.com   
Principal Investigator: Prateep Kanjanavikai, MD         
Sub-Investigator: Siriluk Phanomcheong, MD         
Maharat Nakhon Ratchasima Hospital Not yet recruiting
Nakhon Ratchasima, Nakhon Ratchasrima, Thailand, 30000
Contact: Pichit Puernngoluerm, MD    +6644235000    bank.pichit26@gmail.com   
Contact: Anucha Saeresjittima, MD    +6644235000    anuchasae@gmail.com   
Principal Investigator: Pichit Puernngoluerm, MD         
Sub-Investigator: Anucha Saeresjittima, MD         
Chiang Kham Hospital Recruiting
Chiang Kham, Phayao, Thailand, 56110
Contact: Chaiwat Putiyanun, MD    +6654451300-1    putiyanun@hotmail.com   
Principal Investigator: Chaiwat Putiyanun, MD         
Bhumibol Adulyadej Hospital Recruiting
Bangkok, Thailand, 10220
Contact: Sinart Prommas, MD    +6625347317    n_prommas@hotmail.com   
Contact: Prapaisri Layangool, MD    +6625347306    p_layangool@yahoo.com   
Principal Investigator: Sinart Prommas, MD         
Sub-Investigator: Prapaisri Layangool, MD         
Nopparat Rajathanee Hospital Recruiting
Bangkok, Thailand, 10230
Contact: Orada Patamasingh Na Ayudhaya, MD    +6625174270-9    oradaaom@hotmail.com   
Contact: Anita Luvira, MD    +6625174270-9    aluvira@yahoo.com   
Principal Investigator: Orada Patamasingh Na Ayudhaya, MD         
Sub-Investigator: Anita Luvira, MD         
Prapokklao Hospital Recruiting
Chantaburi, Thailand, 22000
Contact: Prapap Yuthavisuthi, MD    +6639324975 ext 5253    yuthavisuthi@gmail.com   
Contact: Chaiwat Ngampiyasakul, MD    +6639324975 ext 5253    chaiwat008@gmail.com   
Principal Investigator: Prapap Yuthavisuthi, MD         
Sub-Investigator: Chaiwat Ngampiyasakul, MD         
Nakornping Hospital Recruiting
Chiang Mai, Thailand, 50180
Contact: Aram Limtrakul, MD    +6653999200    aramlim@hotmail.com   
Contact: Arunrat Suwannarat, MD    +6653999200    arunrat11@yahoo.com   
Principal Investigator: Aram Limtrakul, MD         
Sub-Investigator: Arunrat Suwannarat, MD         
Health Promotion Center Region 10 Recruiting
Chiang Mai, Thailand, 50100
Contact: Suraphan Sangsawang    +6653272740    suraphan@anamai.moph.go.th   
Contact: Kanokwan Jittayanun    +6653272740    kkulsawad@yahoo.co.th   
Principal Investigator: Suraphan Sangsawang, MD         
Sub-Investigator: Kanokwan Jittayanun, MD         
Chiangrai Prachanukroh Hospital Recruiting
Chiang Rai, Thailand, 57000
Contact: Jullapong Achalapong, MD    +6653711300 ext 1217    drjullapong@gmail.com   
Contact: Chulapong Chanta, MD    +6653711300 ext 1274    Chul_chan@yahoo.com   
Principal Investigator: Jullapong Achalapong, MD         
Sub-Investigator: Chulapong Chanta, MD         
Chonburi Regional Hospital Recruiting
Chonburi, Thailand, 20000
Contact: Nantasak Chotivanich, MD    +6638931390    nantasak.cho@gmail.com   
Contact: Chureeratana Bowonwatanuwong, MD    +6638274200    c.bowon@gmail.com   
Principal Investigator: Nantasak Chotivanich, MD         
Sub-Investigator: Suchat Hongsiriwon, MD         
Sub-Investigator: Chureeratana Bowonwatanuwong, MD         
Khon Kaen Hospital Recruiting
Khon Kaen, Thailand, 40000
Contact: Thitiporn Siriwachirachai, MD    +6643336789    siriwachirachai@hotmail.com   
Contact: Ussanee Srirompotong, MD    +6643336789      
Principal Investigator: Thitiporn Siriwachirachai, MD         
Sub-Investigator: Ussanee Srirompotong, MD         
Lampang Hospital Recruiting
Lampang, Thailand, 52000
Contact: Prateung Liampongsabuddhi, MD    +6654223623-7    prateung@yahoo.com   
Contact: Kultida Pongdetudom, MD    +6654223623-7    pongdetudom@yahoo.com   
Principal Investigator: Prateung Liampongsabuddhi, MD         
Sub-Investigator: Kultida Pongdetudom, MD         
Lamphun Hospital Recruiting
Lamphun, Thailand, 51000
Contact: Wanmanee Matanasarawut, MD    +6653569100 ext 2150    obgyn.lph@gmail.com   
Contact: Rosalin Somsamai, MD    +6653569100    sukannika_waan@hotmail.com   
Principal Investigator: Wanmanee Matanasarawut, MD         
Sub-Investigator: Rosalin Somsamai, MD         
Phayao Provincial Hospital Recruiting
Phayao, Thailand, 56000
Contact: Pornnapa Suriyachai, MD    +6654431209    whan76_1@hotmail.com   
Contact: Pornchai Techakunakorn, MD    +6654431169    pcaipyhos@gmail.com   
Principal Investigator: Pornnapa Suriyachai, MD         
Sub-Investigator: Pornchai Techakunakorn, MD         
Sub-Investigator: Guttiga Halue, MD         
Samutprakarn Hospital Recruiting
Samutprakarn, Thailand, 10280
Contact: Prapan Sabsanong, MD    +6627018132-9    prapandr@hotmail.com   
Contact: Parichart Wongngam, MD    +6627018132-9      
Principal Investigator: Prapan Sabsanong, MD         
Sub-Investigator: Parichart Wongngam, MD         
Samutsakhon Hospital Recruiting
Samutsakorn, Thailand, 74000
Contact: Supang Varadisai, MD    +6634427099-104    supang_vara@hotmail.com   
Contact: Sawitree Krikajornkitti, MD    +6634427099-104    yuiwitree@gmail.com   
Principal Investigator: Supang Varadisai, MD         
Sub-Investigator: Sawitree Krikajornkitti, MD         
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Gilead Sciences
Investigators
Principal Investigator: Gonzague Jourdain, MD, PhD Institut de Recherche pour le Developpement
  More Information

Publications:
Responsible Party: Gonzague Jourdain, Chargé de recherches, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT01745822     History of Changes
Other Study ID Numbers: U01HD071889, U01HD071889
Study First Received: December 6, 2012
Last Updated: February 25, 2014
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
Hepatitis B
Hepatitis B sAg
Hepatitis B eAg
pregnancy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 19, 2014