A Pilot Study Evaluating the Combination Hepatitis A and B Vaccine (Twinrix®) in Healthy Healthcare Workers Who Meet the CDC Definition for Non-responders.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Protective immunity to Hepatitis B
研究概览
简要总结
Hepatitis B is a vaccine preventable infection which can be transmitted through occupational exposure. Approximately 15% of patients will not respond to an initial series of vaccination. Of those re-vaccinated approximately fifty percent will respond. On the basis of poor response to a third series, repeat vaccination is not recommended and non-responders are considered vulnerable to infection. Cardell studied the use of double dose combination hepatitis A and B vaccine (Twinrix) in non responders who had received four or more doses previously and found a high response rate suggesting this vaccine and dose could be effective. The investigators study seeks to duplicate the findings of Cardell, using a more strict definition of non-responder (6 or more previous doses).
详细描述
Hepatitis B is a blood borne infection that is highly transmissible through occupational exposure in healthcare. The maximal risk for transmission occurs with needle-stick injuries. However, the majority of cases of transmission probably occur with lower risk exposures. Overall, the risk of transmission of hepatitis B from an infected patient to a susceptible health care worker is estimated at 23-62% after a single parenteral exposure (US PHS 2001).
Acute hepatitis B is symptomatic in approximately 30% of cases, with 0.1-0.5% of these cases developing fulminant hepatitis with a risk of death. Another 5% of cases will go on to chronic hepatitis B infection with an associated risk of cirrhosis and hepatocellular carcinoma.
This transmission can be prevented by vaccination of health care workers prior to exposure. Successful vaccination can provide years of protection (Alavian 2008) Consequently, the US CDC and the Canadian National Advisory Committee on immunization recommends vaccination for all heath care workers who will have contact with blood, bodily fluids, or sharps. A test for immunity should be performed after completion of vaccination, because ~15% of healthy adults do not respond to a primary vaccine series.
For those health care workers who are not immune after a first series, a second immunization attempt should be made. The expected rate of response in this group is 30-50% (US PHS 2001).Those who fail to develop a protective antibody response (anti-hepatitis B surface antigen antibody titre of >=10mIU/ml), are labelled non-responders and should be considered susceptible to infection. A third attempt at vaccination is currently not recommended because the estimated rate of response is only 10%.
When susceptible, vaccine non-responding health care workers have an occupational exposure to hepatitis B, the CDC recommends treatment with two doses hepatitis B immune globulin, a blood product which has an undefined risk of transmitting yet unknown blood borne infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Have an understanding of the study, agree to its provisions, and give written informed consent prior to study entry.
- •Available for follow-up during the study period.
- •Has had at least two complete courses of monovalent hepatitis B vaccine, and has documented antiHbS IgG titers of <10mIU/ml within 6 months of completion of the most recent course of vaccination.
排除标准
- •Allergic to any components of the vaccine.
- •Previous serious adverse events associated with the hepatitis B vaccine
- •Received one or more doses of Twinrix in the past
- •Chronic hepatitis B infection, defined as ever having had a positive HBSAg, HBCAb or HepB RNA test
- •Pregnant, or planning to become pregnant during the study period.
- •Received dose of hepatitis B immune globulin, or immune globulin, in last 6 months
- •Immunocompromising condition or therapy that would be expected to reduce the efficacy of vaccination, including:
- •HIV infection;
- •lymphoma, multiple myeloma, leukemia or other blood dyscrasia;
- •systemic lupus erythematosis or other connective tissue disorder;
- •renal failure (baseline serum creatinine >150uM, or requires dialysis);
- •nephrotic syndrome;
- •active neoplastic disease (except localized skin cancer);
- •any requirement for corticosteroids >20mg/day for >1 week in the six months prior to randomization;
- •cytotoxic therapy (e.g. chemotherapy for cancer) received within the six months prior to randomization
- •radiation therapy received in the six months prior to randomization;
- •hemoglobinopathy;
- •any immunodeficiency disorder; or
- •prior solid organ or allogeneic stem cell or bone marrow transplant.
- •Plans to receive cytotoxic therapy or radiation therapy during the study period.
结局指标
主要结局
Protective immunity to Hepatitis B
时间窗: up to 7 months (average)
The number of patients who develop protective antibody titres (\>10 mIU/ml) during the immunization period. This will be followed 1 month after each dose received.
次要结局
- Partial immunity to Hepatitis B(up to 7 months (average))
- Rate of Recruitment(1 year)
- Adverse Events(up to 7 months (average))
研究者
Allison McGeer
Professor
Mount Sinai Hospital, Canada