Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand (iTAP)
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|ClinicalTrials.gov Identifier: NCT01745822|
Recruitment Status : Completed
First Posted : December 10, 2012
Last Update Posted : June 14, 2019
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 or disease||Intervention/treatment||Phase|
|Hepatitis B Chronic Infection Pregnancy||Drug: tenofovir disoproxil fumarate Drug: placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||328 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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.|
|Study Start Date :||January 2013|
|Actual Primary Completion Date :||December 2016|
|Actual Study Completion Date :||October 2018|
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
Placebo Comparator: Placebo
matching placebo (of tenofovir disoproxil fumarate)
administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
- Infant's Hepatitis B infection status at 6 months of age [ Time Frame: 6 months of age ]Infection is defined as HBsAg positive confirmed by HBV DNA
- Adverse events [ Time Frame: from enrollment (28 weeks' gestation) to 12 months postpartum ]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 ]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 ]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
- Weight, height and head circumference for age [ Time Frame: at 6 months and 12 months of age ]Weight, length/height and head circumference WHO Z scores
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01745822
|Principal Investigator:||Gonzague Jourdain, MD, PhD||Institut de Recherche pour le Developpement|