Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand (iTAP)
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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. |
- Infant's Hepatitis B infection status, defined as HBsAg positive confirmed by HBV DNA [ Time Frame: 6 months of age ] [ Designated as safety issue: No ]
- Occurrence of maternal and infant adverse events (AE), including ICH Maternal and Infants Serious Adverse Events and DAIDS grade 3/4 signs and symptoms, regardless of their relatedness to the study treatment. [ Time Frame: from enrollment to 12 months postpartum ] [ Designated as safety issue: Yes ]
- Occurrence of acute exacerbation of hepatitis B after study treatment interruption [ Time Frame: Following planned discontinuation of study treatment up to 12 months postpartum ] [ Designated as safety issue: Yes ]The acute exacerbation or flare of hepatitis B is defined as ALT more than 10 times Upper Limit of Normal (ULN) and more than twice the baseline value
- Infant's HBV infection status, defined as HBsAg positive confirmed by HBV DNA, [ Time Frame: at or after 6 months through 12 months of age ] [ Designated as safety issue: No ]
- 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
tenofovir disoproxil fumarate, 300 mg tablets
|
Drug: tenofovir disoproxil fumarate
administration: once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Other Names:
|
|
Placebo Comparator: Placebo
matching placebo
|
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 or 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 |
Inclusion Criteria:
- Pregnancy
- At least 18 years of age
- Negative Human Immunodeficiency Virus (HIV) serology
- Positive HBsAg and HBeAg tests
- Gestational age of 28 weeks (+ or - 10 days) as determined by obstetrician
- ALT ≤30 U/L
- 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 anti-HBV antiviral treatment
- 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| Contact: Gonzague Jourdain, MD, PhD | +66818830065 | Gonzague.Jourdain@ird.fr |
| Contact: Nicole Ngo-Giang-Huong, PharmD, PhD | +66898511178 | Nicole.Ngo-Giang-Huong@ird.fr |
| Thailand | |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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: | January 3, 2013 |
| 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 Hepatitis, Viral, Human Hepatitis, Chronic Liver Diseases Digestive System Diseases Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections |
DNA Virus Infections 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 June 17, 2013