Randomized, Double-blind, Placebo-controlled Trial, to Evaluate the Safety and Immunogenicity of Orally Administered, Killed, Bivalent Whole-cell, Cholera Vaccine, ShanChol in Bangladeshi Adults and Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 330
- 试验地点
- 2
- 主要终点
- Safety and Reactogenicity: of orally administered killed, bivalent whole-cell cholera vaccine cholera vaccine, ShanChol
研究概览
简要总结
Background: Severe dehydrating cholera due to V. cholerae O1 is an important public health problem in Bangladesh and many other developing countries. V. cholerae O1 is a major bacterial pathogen causing around 5 million cases and at least 200,000 deaths in adults and children each year. It can be assumed that there are at least 300,000 severe cases and 1.2 million infections in people in Bangladesh alone. The rate of cholera varies from around 1 to 8 per 1000 population and the highest attack rate is in children 2- to 9-year years of age . Cholera is now also being documented in very young children. Currently enteric vaccine approaches are regarded as the most accessible short term and practical means to prevent and control such illnesses to prevent disease and epidemics in resource poor settings with limited public health and sanitary facilities.
An effective inactivated whole cell bivalent cholera vaccine against Vibrio cholerae O1 and O139 was produced and implemented for public health purposes in Vietnam since the 1990s. This bivalent vaccine has been found to be safe and to confer significant protection against El Tor cholera in both children and adults and has over the last decade being used in the Vietnam to protect against cholera. This vaccine has further been reformulated by the IVI to meet WHO requirements and is now being produced in WHO prequalified vaccine company in India.
The reformulated vaccine has been shown to be safe and immunogenic in Indian children as well as adults. A large Phase III study of the vaccine, has recently been carried out in Kolkata, India in over 120,000 participants aged from one year and above. Results of the study are encouraging and the vaccine gives over 60% protection against cholera. The vibriocidal antibody response rate was 80% in children and 53% in adults. Following this study, the vaccine, designated as ShanChol has been licensed in India in April 2009. The vaccine is now being marketed in India and is available at a cost affordable for developing country settings.
Objective: The aim of the proposed study is to assess if the orally administered, killed, bivalent whole-cell cholera vaccine, ShanChol will be safe and immunogenic in different age groups in Bangladesh in children and adults.
Study design: This will be a randomized, double blind, placebo-controlled study on a total of 330 subjects, 165 vaccine and 165 placebo recipients. The specific aims will be to determine: i) safety and determine adverse events if any (ii) determine immune responses.
Relevance: The study of ShanChol on Bangladeshi children and adults will be able to give information regarding the safety and immunogenicity of the vaccine in Bangladeshi subjects. This information will be important for proceeding with larger studies in Bangladesh and if proven useful for introduction the cholera vaccine in the country in the future.
详细描述
Adults as well as children, both males and females will be recruited in the study from the urban suburbs around Dhaka city in Mirpur where we have been conducting other epidemiological and vaccine related studies. The community will be informed by our field staffs and interested persons might be enrolled in the study on the basis of inclusion/exclusion criteria.
Part I- Adults- 18-45 years of age (n=110):
Since this oral bivalent whole-cell cholera vaccine has not been tested in Bangladesh before, the study will be carried out in 3 age groups, i.e. adults, followed by toddlers and younger children. These study participants will be recruited from the field site in Mirpur. For this purpose, 55 adults (18-45 year old) will be given 2 doses of the bivalent whole-cell cholera vaccine and 55 adults will be given placebo. Safety will be clinically monitored for side effects for 3 days after each dose of study agent by home visits. Participants will be randomized to receive either 2 doses of the vaccine or placebo, given 14 days apart.
Part II- Children 2-5 years (n=110):
If the vaccine is found safe in the adult study, it will be tested in the toddlers in the field consisting of 55 children in each group. The children will be clinically monitored for side effects for 3 days after each dose of vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Months 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 12-23 months for younger children group, 2-5 years for the toddler group and 18-45 years for the adult group.
- •Sex: Either
- •Consent: Written informed consent from study participants and parents in case of children.
- •Compliance to study procedures: e.g. available for follow-up visits and agrees to specimen collection.
- •Apparently healthy: as determined by medical history, physical examination findings, and clinical judgment of the study physician.
排除标准
- •Chronic disease: history or evidence of chronic illness.
- •Gastrointestinal symptoms such as abdominal pain or cramps, loss of appetite, nausea, general ill-feeling or vomiting in the past 24 hours or abdominal pain lasting for more than 2 weeks in the past 6 months
- •Intake of any anti-diarrheal medicine or antimicrobial therapy the past week.
- •Acute disease one week prior to enrollment, with or without fever ≥38ºC .
- •Receiving of cholera vaccine any time in the past, and any other live or killed enteric vaccine in the last 4 weeks.
- •Diarrhea within 6 week period at screening.
结局指标
主要结局
Safety and Reactogenicity: of orally administered killed, bivalent whole-cell cholera vaccine cholera vaccine, ShanChol
时间窗: 1 year
次要结局
- Immunogenicity: of cholera vaccine assessed by serum vibriocidal antibody responses as well as serological and mucosal responses to vaccine antigens and compare it with those obtained with placebo recipients.(1 year)