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

NCT01745822 | Completed Phase 3 Results DMC

• 1 other identifier: U01HD071889
• Study Type: interventional
• Target: 654
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Hepatitis B Chronic Infection; Pregnancy

Keywords

Hepatitis B; Hepatitis B sAg; Hepatitis B eAg; pregnancy

Outcome Measures

Primary Outcomes (1)

• Percentage of Infants With Hepatitis B Infection at 6 Months of Age

  Infection is defined as a HBsAg positive test confirmed by detectable HBV DNA

  6 months of age

Secondary Outcomes (4)

• Percentage of Participants With Adverse Events

  from enrollment (28 weeks' gestation) to 12 months postpartum

• Percentage of Participants With Flares After Study Treatment Interruption

  Following planned discontinuation of study treatment up to 12 months postpartum

• Percentage of Infants With Hepatitis B Infection at or After 6 Months Through 12 Months of Age

  at or after 6 months through 12 months of age

• Weight, Height and Head Circumference for Age

  assessed at 6 months and 12 months of age, 6 months reported

Study Arms (2)

Tenofovir disoproxil fumarate

EXPERIMENTAL

tenofovir disoproxil fumarate, 300 mg tablets

Drug: tenofovir disoproxil fumarate

Placebo

PLACEBO COMPARATOR

matching placebo (of tenofovir disoproxil fumarate)

Drug: placebo

Interventions

tenofovir disoproxil fumarate DRUG

administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum

Also known as: Viread, TDF, tenofovir

Tenofovir disoproxil fumarate

placebo DRUG

administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut de Recherche pour le Developpement: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Centers for Disease Control and Prevention: collaborator
• Gilead Sciences: collaborator

Study Sites (17)

Banglamung Hospital

Bang Lamung, Changwat Chon Buri, 20150, Thailand

Location

Chiang Kham Hospital

Chiang Kham, Changwat Phayao, 56110, Thailand

Location

Mae Chan Hospital

Mae Chan, Chiangrai, 57110, Thailand

Location

Maharat Nakhon Ratchasima Hospital

Nakhon Ratchasima, Nakhon Ratchasrima, 30000, Thailand

Location

Bhumibol Adulyadej Hospital

Bangkok, 10220, Thailand

Location

Nopparat Rajathanee Hospital

Bangkok, 10230, Thailand

Location

Prapokklao Hospital

Chanthaburi, 22000, Thailand

Location

Health Promotion Center Region 10

Chiang Mai, 50100, Thailand

Location

Nakornping Hospital

Chiang Mai, 50180, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiang Rai, 57000, Thailand

Location

Chonburi Regional Hospital

Chon Buri, 20000, Thailand

Location

Khon Kaen Hospital

Khon Kaen, 40000, Thailand

Location

Lampang Hospital

Lampang, 52000, Thailand

Location

Lamphun Hospital

Lamphun, 51000, Thailand

Location

Samutprakarn Hospital

Mueang Samut Prakan, 10280, Thailand

Location

Phayao Provincial Hospital

Phayao, 56000, Thailand

Location

Samutsakhon Hospital

Samut Sakhon, 74000, Thailand

Location

Related Publications (10)

• Jourdain G, Ngo-Giang-Huong N, Cressey TR, Hua L, Harrison L, Tierney C, Salvadori N, Decker L, Traisathit P, Sirirungsi W, Khamduang W, Bowonwatanuwong C, Puthanakit T, Siberry GK, Watts DH, Murphy TV, Achalapong J, Hongsiriwon S, Klinbuayaem V, Thongsawat S, Chung RT, Pol S, Chotivanich N. 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. BMC Infect Dis. 2016 Aug 9;16:393. doi: 10.1186/s12879-016-1734-5.

  PMID: 27506549 BACKGROUND

• Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Tierney C, Cressey TR, Achalapong J, Siberry GK, Nelson NP, and Chotivanich N. TDF to prevent perinatal hepatitis B virus transmission: a randomized trial (iTAP). Conference on Retroviruses and Opportunistic Infections (CROI) Abstract 584LB; 2017 February 13; Seattle, WA, USA. http://www.croiconference.org/sessions/tdf-prevent-perinatal-hepatitis-b-virus-transmission-randomized-trial-itap

  RESULT

• Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N. Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B. N Engl J Med. 2018 Mar 8;378(10):911-923. doi: 10.1056/NEJMoa1708131.

  PMID: 29514030 RESULT

• Jourdain G, Harrison LJ, Ngo-Giang-Huong N, Cressey TR, Decker L, Tierney C, Achalapong J, Kanjanavikai P, Luvira A, Srirompotong U, Murphy TV, Nelson N, Siberry GK, Pol S, for the iTAP Study Group. iTAP trial: maternal and infant efficacy and safety results 12 months after delivery. CROI, 4-7 March 2018, Boston, USA. #1316, Oral Presentation O-11

  RESULT

• Salvadori N, Fan B, Teeyasoontranon W, Ngo-Giang-Huong N, Phanomcheong S, Luvira A, Puangsombat A, Suwannarat A, Srirompotong U, Putiyanun C, Kourtis A, Bulterys M, Siberry GK, Jourdain G. TDF prophylaxis for PMTCT of HBV: effect on maternal and infant bone mineral density. CROI, 4-7 March 2018, Boston, USA. #1174. Poster and Themed Discussion TD-09

  RESULT

• Cressey TR, Harrison L, Achalapong J, Kanjanavikai P, Patamasingh Na Ayudhaya O, Liampongsabuddhi P, Siriwachirachai T, Putiyanun C, Suriyachai P, Tierney C, Salvadori N, Chinwong D, Decker L, Tawon Y, Murphy TV, Ngo-Giang-Huong N, Siberry GK, Jourdain G; iTAP Study Team. Tenofovir Exposure during Pregnancy and Postpartum in Women Receiving Tenofovir Disoproxil Fumarate for the Prevention of Mother-to-Child Transmission of Hepatitis B Virus. Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01686-18. doi: 10.1128/AAC.01686-18. Print 2018 Dec.

  PMID: 30275094 RESULT

• Salvadori N, Fan B, Teeyasoontranon W, Ngo-Giang-Huong N, Phanomcheong S, Luvira A, Puangsombat A, Suwannarat A, Srirompotong U, Putiyanun C, Cressey TR, Decker L, Khamduang W, Harrison L, Tierney C, Shepherd JA, Kourtis AP, Bulterys M, Siberry GK, Jourdain G. Maternal and Infant Bone Mineral Density 1 Year After Delivery in a Randomized, Controlled Trial of Maternal Tenofovir Disoproxil Fumarate to Prevent Mother-to-child Transmission of Hepatitis B Virus. Clin Infect Dis. 2019 Jun 18;69(1):144-146. doi: 10.1093/cid/ciy982.

  PMID: 30924492 RESULT

• Ngo-Giang-Huong N, Salvadori N, Khamduang W, Cressey TR, Harrison LJ, Decker L, Tierney C, Jullapong A, Murphy TV, Nelson N, Siberry GK, Chung RT, Pol S, Jourdain G. Hepatitis B virus DNA level changes in HBeAg+ pregnant women receiving TDF for PMTCT. Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, 4-7 Mar 2019

  RESULT

• Bukkems V, Smolders E, Jourdain G, Hawkins D, Achalapong J, Kanjanavikai P, Taylor G, Prommas S, Burger D, Colbers A, Cressey TR, for the iTAP Study Team & PANNA network. Tenofovir plasma concentrations in pregnant women: comparison of hepatitis B and HIV-infected patients. 20th International Workshop on Clinical Pharmacology of HIV, Hepatitis & Other Antiviral Drugs. Noordwijk, the Netherlands, 14-16-May 2019

  RESULT

• Jourdain G, Traisathit P, Salvadori N, Wangsaeng N, Khamduang W, Ngo-Giang-Huong N, for the iTAP Study Group. Immunization response in infants born to HBsAg+ and HBeAg+ mothers receiving TDF (ID 3681). Conference on Retroviruses and Opportunistic Infections (CROI), Hynes Convention Center, USA, 8-11 Mar 2020, Virtual Conference

  RESULT

MeSH Terms

Conditions

Hepatitis B

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gonzague Jourdain
• Organization: French National Research Institute for Sustainable Development (IRD)

gonzague.jourdain@ird.fr

+66818830065

Study Officials

• Gonzague Jourdain, MD, PhD

  Institut de Recherche pour le Developpement

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chargé de recherches

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: October 1, 2018
• Last Updated: March 5, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-02

Locations

TH (17)