The Treatment in Pregnancy for Hepatitis C ("TiP-HepC") Registry (TiP-HepC)

December 13, 2024 updated by: The Task Force for Global Health

An Observational Study of Mother-Infant Outcomes Following Antenatal Exposure to Direct-Acting Antivirals: the Treatment in Pregnancy for Hepatitis C ("TiP-HepC") Registry

Clinical interventions to reduce the risk of vertical transmission of hepatitis C virus (HCV) infection from mother to infant are highly limited. Direct-acting antiviral (DAA) medications have demonstrated excellent safety and efficacy in non-pregnant individuals, but there is a lack of data regarding the safety of these medications in pregnant women and the effectiveness of these medications in reducing mother-to-child transmission. Therefore, although HCV screening during pregnancy is now recommended in many countries, there is no approved treatment for HCV during pregnancy. An observational study is here proposed to assess outcomes of mother-infant pairs exposed to DAAs during pregnancy within a global clinical case registry. Data regarding the exposures and outcomes of mother-infant pairs exposed to DAAs during pregnancy will be solicited and collected from clinical providers, healthcare facilities, HCV treatment programs, and other clinical practices worldwide. Data will be shared and maintained within a secure database, and cumulative data will be analyzed at pre-determined six-month intervals. The primary outcome will be the number and proportion of mother-infant pairs with adverse pregnancy or birth outcomes. The results of this study will inform HCV treatment decisions by clinical providers and programs worldwide.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In 2016, approximately 6% of all women who were tested for HCV during pregnancy in the United States were HCV antibody-positive. That year, there were 14,417 live births delivered by HCV-positive women, which comprised 0.38% of all live births in the US. Globally, the HCV prevalence among pregnant women varies widely (0.06%-7%) depending on regional and local epidemiology and risk factors. Approximately 5.8% of infants born to HCV-infected mothers will acquire HCV infection with higher rates of transmission among women with HIV co-infection. The primary route for the vertical transmission of HCV is believed to be the perinatal exposure of the infant to maternal blood, though in utero transmission also occurs.

Hepatitis C virus (HCV) testing for pregnant women is now recommended in many countries and universal HCV screening for pregnant women was adopted in the United States in 2020. No clinical interventions have been proven to reduce perinatal HCV transmission, but current and clinical practice guidelines include recommendations for the avoidance of potentially invasive procedures during delivery (ie, chorionic villus sampling, fetal scalp monitoring, episiotomy). The effect of virologic suppression or cure of HCV infection during pregnancy on the risk of mother-to-child HCV transmission has not been directly studied. Previous HCV treatment regimens were contra-indicated in pregnancy due to the inclusion of ribavirin and other teratogenic drugs. More recently, interferon- and ribavirin-free direct-acting antiviral (DAA) medications have raised the potential for HCV treatment during pregnancy to prevent perinatal transmission of HCV and allow for treatment of women during pregnancy. Over half of women reported a preference for HCV treatment during pregnancy if it reduced the probability of vertical transmission to the infant. In addition to potentially reducing vertical transmission to the infant during the current pregnancy, treatment during pregnancy can increase the number of women treated for HCV, and decrease the likelihood of being infected during subsequent pregnancies. Many vulnerable women are at high-risk for loss-to-follow-up following delivery and many women living with HCV may only be eligible for health insurance during pregnancy and immediately postpartum.

Several DAA regimens have demonstrated excellent safety and efficacy profiles in non-pregnant individuals across multiple or all HCV genotypes, achieving cure in >95% of people in as few as 8 weeks of once-daily oral treatment. However, there are limited data regarding the safety and efficacy of DAAs in pregnancy. A phase I pharmacokinetic study of sofosbuvir/ledipasvir (SOF/LDV) in 9 pregnant women demonstrated similar drug levels to non-pregnant individuals with excellent safety and efficacy profile, and a similar study of sofosbuvir/velpatasvir (SOF/VEL) is currently enrolling participants. A prospective study of 15 women treated with SOF/LDV in India reported no adverse events. No other trials have been conducted or registered for pregnant individuals to date. The frequency and outcomes for women who become pregnant while on DAA treatment have been rarely reported. Currently, there is only one published study reporting outcomes of mother-infant pairs of women who became pregnant while on DAA treatment; among 100 women, 9 of whom completed 12 weeks of treatment with various regimens, no major adverse events were reported.

Given the paucity of data regarding the safety and efficacy of DAA treatment in pregnancy, the American College of Obstetrics and Gynecology and Society for Maternal-Fetal Medicine recommend that DAAs "only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a direct-acting antiviral should be counseled in a shared decision-making framework about the risks and benefits of continuation." The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases (IDSA/AASLD) advise that "treatment can be considered during pregnancy on an individual basis after a patient-physician discussion about the potential risks and benefits". Treatment for HCV in pregnancy therefore remains an off-label use of DAA medications and clinical practices remain highly variable by providers and programs. The frequency, geographic distribution, safety profile or effectiveness of HCV treatment during pregnancy for mother-infant pairs have not been evaluated or reported.

The primary objective of this observational study is to assess the safety of DAA treatment in mother-infant pairs with exposure to DAA medications during pregnancy within a clinical case registry. The secondary objectives of this study are to describe the frequency and distribution of known cases of DAA exposure during pregnancy and to assess the effectiveness of DAA treatment in pregnancy in achieving HCV cure for mothers and reducing the transmission of HCV from mother to infant.

This is an observational study of the outcomes of mother-infant pairs exposed to DAA treatment during pregnancy in routine clinical practice using de-identified data from a convenience sample of health facilities, public health, government, and private entities globally. Data regarding the demographics, baseline clinical status, timing and type of DAA exposure, and pregnancy/birth outcomes of mother-infant pairs exposed to DAAs during pregnancy will be solicited from clinical providers, health facilities, HCV treatment programs, and other clinical practices or programs prescribing DAA treatment. Data will be coded, standardized, and pooled in a common database for analysis.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30030
        • Recruiting
        • The Taskforce for Global Health
        • Contact:
        • Contact:
          • John Ward, MD
        • Contact:
          • Neil Gupta, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Individuals with chronic HCV infection and documented pregnancy

Description

Inclusion Criteria:

-Documented pregnancy with: Estimated date of conception by documentation of either 1) date of last menstrual period or 2) ultrasound evaluation Actual date of delivery

  • Documented chronic HCV infection prior to or during pregnancy (positive test for HCV RNA or HCV core antigen)
  • Documented DAA exposure occurring within 30 days of the estimated date of conception and before the pregnancy outcome (ie, fetal demise, spontaneous abortion, live delivery, etc). Eligible DAA drugs are listed in Appendix 1.

Exclusion Criteria:

- DAA exposures that include ribavirin or interferon will be excluded given their established harm during pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse pregnancy outcomes
Time Frame: 1 year
The primary outcomes measured in the study are adverse pregnancy and birth outcomes documented at the time of the outcome of the pregnancy (primary endpoint). Primary adverse pregnancy outcomes include preterm delivery (<37 weeks gestational age), stillbirth or fetal demise, and maternal death.
1 year
Number of adverse birth outcomes
Time Frame: 1 year
Primary adverse birth outcomes include low birth weight (<2500g), small for gestational age, need for neonatal intensive care, and presence of congenital anomaly.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of registry participants achieving SVR12
Time Frame: 12 weeks
Secondary outcomes of the study are the proportion of women achieving HCV cure by HCV PCR test 12 weeks following last DAA treatment (SVR12)
12 weeks
Proportion of infants with HCV infection
Time Frame: 18 months
proportion of infants with evidence of chronic HCV infection after 2 months of age by HCV PCR or after 18 months of age by anti-HCV antibody seropositivity
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Task Force for Global Health

Collaborators

Centers for Disease Control and Prevention

Investigators

  • Principal Investigator: John Ward, MD, The Taskforce for Global Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 30, 2026

Study Registration Dates

First Submitted

April 26, 2022

First Submitted That Met QC Criteria

May 6, 2022

First Posted (Actual)

May 10, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 13, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00083175

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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