Comparison the Seroconversion Rate Between Two-dose and Three-dose Regimens of Heplisav B Among Patients With Cirrhosis, a Randomized-control Prospective Study.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- The rates of seroconversion after two doses of Heplisav-B given at 0 and 4 weeks versus three doses of Heplisav-B given at 0, 4 weeks, and 8 weeks.
研究概览
简要总结
Investigators want to compare the seroconversion rates between two-dose and three-dose regimens of the hepatitis B vaccine (Heplisav B) among patients with cirrhosis, a randomized prospective study.
详细描述
Study Rationale:
Hepatitis B virus is a major cause of acute and chronic liver disease both in the United States and worldwide. In 2016, an estimated 862,000 people were living with HBV infection in the US with a total of 1,649 U.S. death certificates recorded as an underlying or contributing cause of death. Chronic infection may cause liver cirrhosis and hepatocellular carcinoma (HCC). Since the introduction of the vaccine in the 1990s, there has been a significant decline in the incidence of HBV infection. Approved in November 2017, Heplisav-B uses a synthetic cytosine phosphoguanine oligonucleotide derived from bacterial DNA; it is thought to stimulate the immune system through activation of the toll-like receptor 9 pathway, which induces the production of cytokines such as interleukines such as interleukine-12 and interferon-alpha. It has been shown to induce higher immunity in healthy individuals compared to conventional vaccines.
The HBsAb titer should be checked 8 to 12 weeks after the administration of the vaccination series. Good responders were defined as those having the anti-HBs titer were ≥ 100 mUI/ml, poor responders having anti-HBs titer between 10 and 99 mUI/ml, and nonresponders having anti-HBs titer < 10 mIU/ml. The Seroprotection rate by age group in the healthy population is 100% in the 18-29-year-old group, 98.9% in the 30-29 %-year-old group, 97.2% in the 40-49-year-old group, 95.2% in the 50-59-year-old group, 91.6% in 60-70-year-old group. However, 5% of the general population will not mount a protection response.
Response to HBV vaccine is variable among patients with chronic diseases, such as HIV infection, celiac disease, IBD, end-stage renal disease, diabetes. The immunogenicity of the hepatitis B vaccine is also lower in decompensated cirrhosis. Among cirrhotic patients, only 45% who received Heplisav-B achieved immunity in investigator's previous retrospective analysis. The usual approach to HBV vaccine nonresponse is repeating the vaccine series in noninfected individuals.
Investigational Plan
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All the cirrhosis patients more than 18 years old presented to the hepatology clinic in Mercy Medical Center between 09/2020 and 07/2021 who do not have immunity against Hepatitis B (defined as anti-HBs titer < 10 mIU/ml) will be recruited.
排除标准
- •Anyone who has had a serious allergic reaction to a prior dose of the hepatitis B vaccine, a component of the hepatitis B vaccine, or yeast should not receive the hepatitis B vaccine.
- •Those who had previous exposure to hepatitis B.
- •Post liver transplant patients.
- •Less than 18 years old.
研究组 & 干预措施
Cirrhosis, 3-dose regimen
Investigators will randomize the patient in the cirrhotic group to receive a 3-dose regimen of Heplisav-B.
干预措施: Heplisav-B Injectable Product, 3-dose regimen (Biological)
Cirrhosis, 2-dose regimen
Investigators will randomize the patient in the cirrhotic group to receive a 2-dose regimen of Heplisav-B.
干预措施: Heplisav-B Injectable Product, 2-dose regimen (Biological)
Non cirrhosis, 3-dose regimen
Investigators will randomize the patient in the noncirrhotic group to receive a 3-dose regimen of Heplisav-B.
干预措施: Heplisav-B Injectable Product, 3-dose regimen (Biological)
Non cirrhosis, 2-dose regimen
Investigators will randomize the patient in the noncirrhotic group to receive a 2-dose regimen of Heplisav-B.
干预措施: Heplisav-B Injectable Product, 2-dose regimen (Biological)
结局指标
主要结局
The rates of seroconversion after two doses of Heplisav-B given at 0 and 4 weeks versus three doses of Heplisav-B given at 0, 4 weeks, and 8 weeks.
时间窗: 12 weeks after completing Heplisav-B series with two doses or three doses
The rates of seroconversion is defined as an HBsAg antibody concentration ≥ 10 mIU/ml.
次要结局
- Factors are associated with a lower likelihood of achieving immunogenicity, such as age, race, MELD scores, etiologies of cirrhosis, comorbidity, immunosuppressive drugs. Those information will be measured or described descriptively by chart review.(Through study completion, an average of 1 year)