Evaluation of the Natural History and Vertical Transmission of Chronic Hepatitis C Virus Infection in Pregnancy With Targeted Elimination by Postpartum Treatment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Evaluate the rate of vertical transmission
研究概览
简要总结
This is a multicenter, non-comparative, observational study that will recruit women with singleton pregnancy and chronic HCV infection to determine the natural history of chronic HCV in pregnancy and the rate of vertical transmission to their infants. All participants will be offered curative therapy with sofosbuvir/velpatasvir (Epclusa ®) after delivery and the cessation of breastfeeding. Subjects may be enrolled at any time after conception up through 36 weeks gestation. The management of subjects in pregnancy will be in accordance with ACOG guidelines and individual clinical judgment, however testing will include, but not be limited to, testing for HCV infection, HIV infection, HBV infection, HSV infection, group B Streptococcal colonization, HCV genotype, HCV viral load, as well as assessment of hepatic and renal function. Subjects will be followed on a schedule that is determined by their obstetric care providers throughout their pregnancy. Following delivery, infants will be evaluated at 12, 24 and 48 weeks of age, with testing for HCV RNA to be obtained at each evaluation. Vertical transmission is defined as two positive HCV RNA PCR tests, at least one before the 48 week infant visit, and again at the 12-month follow-up infant visit.
详细描述
The treatment of chronic hepatitis C virus infection has dramatically advanced in recent years, with the availability of multiple interferon-free treatment regimens that result in cure in over 95% of treatment naïve individuals with 8 -12 weeks of therapy. Despite these advances, however, the natural history and treatment of HCV remains undefined in several populations, including pregnancy. In particular, rates of vertical (mother to child) transmission, perinatal and neonatal morbidity, assessment of disease severity (fibrosis) in pregnancy and timing of treatment are not well understood.
At least 2.3 million people in the United States and 185 million people worldwide are believed to have chronic HCV infection, although as it is frequently asymptomatic until the development of end-stage liver disease (ESLD), this may be a significant underestimate. Between 2012 and 2014 the HCV detection rate among women of childbearing age increased by 22% nationally and over 200% in Kentucky, while the proportion of children born to HCV infected women increased 68% nationally and 128% in Kentucky.
Currently, in the United States, the overall rate of children born to HCV infected women is 3.4 per 1,000 live births, with the highest rate in West Virginia, with 22.4 per 1,000 live births occurring to HCV-infected women. Overall, the number of HCV infected reproductive age women has doubled from 2006 to 2014, with an estimated 29,000 HCV infected women giving birth and 1,700 infants vertically infected each year, according to previous estimates of vertical transmission.The true incidence of vertical transmission of HCV is unknown, although the most commonly cited meta-analysis reported a mean transmission rate of 5.8% in HIV-negative women and 10.8% in HIV-positive women.
The timing of vertical transmission is also not well characterized. There is limited data regarding the course of chronic hepatitis C during pregnancy, HCV viral loads appear to peak during third trimester. Both utero and peripartum transmission appear possible, while breastfeeding does not appear to be a risk factor. It appears that between 80 and 90% of children who acquire hepatitis C via vertical transmission will develop chronic infection. However, as sequelae of infection are not commonly observed in childhood, and appropriate testing of exposed children is poor, this may not be a true reflection of actual prevalence.
The current AASLD/IDSA HCV Guidelines recommend all children born to HCV infected women be tested, but they do not specify when or in what manner.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18 or older
- •Chronic HCV infection, as defined by positive HCV antibody with confirmation of positive HCV RNA PCR at least 6 months apart, per 2017 AASLD/IDSA criteria. Infection with any genotype (including mixed genotypes) is permitted.
- •If the diagnosis of chronic HCV is not established by two positive viral load (RNA PCR) tests 6 months apart, subjects may be enrolled and followed until the 6-month test is performed. If the follow-up viral load test is negative (i.e. the woman had acute infection that has cleared), the participant will be excluded from further study participation. All participants excluded for this reason will be replaced.
- •Singleton pregnancy, up to and including 36 weeks' gestation, as documented by fetal ultrasound at any time during the pregnancy.
- •Willing and able to understand and sign the informed consent form
- •Willing and able to sign release of Information forms for their own medical and obstetric care and for their infant's neonatal and pediatric care for one year following delivery, or when the last study viral load test is performed, whichever comes later.
排除标准
- •Co-infection with chronic hepatitis B.
- •Active injection drug use, defined as the parenteral use of any substance for non-medicinal purposes in the previous 60 days. Potential subjects who have a history of active injection drug use will be referred to both syringe services programs to prevent the acquisition of HIV and HBV and to substance abuse treatment. Potential subjects who have injected within the last 60 days may be re-screened if they participate in a drug treatment program, subject to the discretion of the investigator.
- •Decompensated cirrhosis, as determined by clinical history or examination
- •Any major medical comorbidity that may confound assessment, such as cardiomyopathy, pulmonary hypertension, type 1 diabetes mellitus or similar serious medical conditions at the discretion of the investigator. Gestational diabetes mellitus or co-infection with HIV are not criteria for exclusion.
研究组 & 干预措施
Pregnant Women with Hep C
SOF/VEL Therapy-sofosbuvir 400mg, velpatasvir 100mg, once daily for 12 weeks at 24 weeks post partum
干预措施: SOF/VEL- sofosbuvir 400mg and velpatasvir 100mg (Drug)
结局指标
主要结局
Evaluate the rate of vertical transmission
时间窗: 12 months of age
Evaluate the rate of vertical transmission in infants born to HCV infected mothers by detection of HCV RNA in the infant prior to and again at 12 months of age.
次要结局
- SVR12(12 weeks post treatment)
- Presence and severity of NAS/NOWS(12 weeks of age)
- Cholestasis of pregnancy(12 weeks post partum)
- Pre-Term Birth(12 weeks post partum)
- Low Birth Weight(12 weeks of age)
研究者
John Cafardi
Dr. John Cafradi, MD, Infectious Disease Specialist
The Christ Hospital