TDF Medicine to Prevent Mother to Child Transmission of Hepatitis B

Hepatitis B Clinical Trial

— TDF  

Official title:

Prevention of Mother-to-child Transmission of Hepatitis B Virus (PMTCT-HBV): a One Arm, Open Label Intervention Study to Estimate the Optimal Timing of Tenofovir (TDF) in Pregnancy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03167229
• Other study ID #: SMRU1702
• Status: Not yet recruiting
• Phase: Phase 4
• First received: April 24, 2017
• Last updated: December 15, 2017
• Start date: June 1, 2018
• Est. completion date: June 1, 2021

Study information

• Verified date: May 2017
• Source: University of Oxford
• Contact: Rose McGready, MD
• Phone: 0817853585
• Email: rose[@]shoklo-unit.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Our goal is to determine the viral kinetics of HBV DNA reduction in 170 non-Thai pregnant women receiving Tenofovir disoproxil fumarate (TDF) to inform a subsequent RCT. The investigators also aim to determine adherence to daily TDF in pregnancy as new interventions must not only be effective but also safe, feasible and acceptable in the local, and ideally global, context.

Study Design: One arm, open label, Tenofovir treatment intervention study

Study Participants: Non-Thai pregnant women estimated gestation 12-20 weeks and their offspring

Planned Sample Size: 170

Primary Objective To estimate the time to HBV DNA suppression (<100 IU/ml) in 170 HBV DNA positive women who start TDF late in the first or early in the second trimester.

Outcome Measures Time in months to HBV DNA < 100 IU/ml

Secondary Objectives

1. To estimate the proportion of women with HBV DNA <100 IU/ml at delivery.

2. To estimate the TDF levels at delivery in women who are HBV DNA detectable and undetectable.

3. To monitor safety of TDF in the Thailand-Myanmar border women

4. To address potential barriers to implementing TDF in early pregnancy to PMTCT-HBV.

5. To determine the rate of hepatic flares post-partum.

6. To estimate the proportion of cases of vertical transmission at 2 months of age.

7. Fetal growth monthly ultrasound, infant growth at 1,2,3,6,12 and neurodevelopment at 6 and 12 months

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 170
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 49 Years

Eligibility

Inclusion Criteria:

• The woman is willing and able to give informed consent for participation in the study.

• Hepatitis B infected (HBsAg confirmed positive)

• Female, 16-49 years (inclusive).

• Estimated gestational age of 12-20 weeks at time TDF is started.

• Willing to take TDF daily during pregnancy.

• Plans to deliver at SMRU (Maw KerThai and Wang Pha SMRU ANC).

• Able (in the Investigators opinion) and willing to comply with all study requirements

Exclusion Criteria:

• HIV positive or on immunosuppressive therapy for other illnesses

• elevated creatinine (>1.0 mg/dL)

• abnormal serum phosphate (<2.4 and >4.5 mg/dL)

• history of kidney disease

• History of pregnancy complications, short cervix

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Drug:
• Tenofovir Disoproxil Fumarate
Daily tenofovir 300 mg will be self-administered by the woman and continued until one month post-partum. Discussions about the study drug are ongoing and the investigators aim to have Gilead, the manufacturer of Tenofovir (VireadTM) provides the drug free of charge, however in the event that this is not possible the investigators will then purchase generic TDF. The drug will be delivered directly to the study site at Mae Sot.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time in months to HBV DNA < 100 IU/ml		3 years
Secondary	Proportion of women with HBV DNA < 100 IU/ml at delivery		3 years
Secondary	Mean TDF level at delivery in selected cases: 10-15 women who are HBV DNA detectable and a matched 20-30 women who are undetectable.		3 years
Secondary	Adverse events specified clinically (headache, nausea, vomiting)	To monitor safety of TDF	3 years
Secondary	Laboratory testing (HBV DNA levels, ALT, AST, Cr) and serum phosphate	To monitor safety of TDF	3 years
Secondary	Questionnaires	Adherence by pill counts.	3 years
Secondary	The proportion of women with elevated AST/ALT (defined as >5x baseline or >10x the upper limit of normal)	AST/ALT baseline monthly, delivery and post-partum for 3 months after stopping TDF.	1 years
Secondary	Proportion of infants that are positive for HBsAg and HBV DNA at birth (cord blood) and 2 months of age.	Infant HBsAg and HBeAg in cord blood and HBV DNA from cord blood and HBsAg at 2 months of age	1 years
Secondary	Fetal and infant anthropometry and infant neurodevelopment will be compared to normative data from this population.	Fetal (HC, AC, FL EFW monthly in-utero) and infant anthropometry (body weight, HC, AC at 1,2,3,6,9,12 months), Shoklo Developmental Test at 6, 12 months.	1 years