An Individually Randomized, Placebo-controlled Trial to Measure the Protection Conferred by a Single Dose Regimen of Bivalent, Killed, Whole Cell Oral Cholera Vaccine (Shanchol™) in Dhaka, Bangladesh
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 204,438
- 试验地点
- 1
- 主要终点
- Number of participants with a single dose regimen oral cholera vaccine Shanchol will get protection
研究概览
简要总结
Bangladesh remains endemic for cholera, which experiences biannual outbreaks with additional epidemics seen during times of floods, cyclones or any natural disaster. It affects all age groups with the majority of fatal cases occurring in children . Therefore, immunization against cholera remains an important public health component in the prevention and control of the disease .The current two-dose regimen of the internationally available oral cholera vaccines (OCV) create a logistical and programmatic challenge for use in national programs or during epidemics ,so it is important to determine if a single dose vaccine will be protective in regions where cholera is endemic. If the vaccine is found to be efficacious following a single dose, this will have profound implications for the use of the vaccine in areas with limited resources particularly in complex emergencies where a multiple dose regimen is difficult to deploy. A single-dose regimen of this vaccine will improve its 'field ability' and allow the vaccine to be used for outbreak control, especially in difficult settings where the risk of cholera is extremely high and provisions for clean water and sanitation are not available. With low OCV production rates, larger populations could be immunized against cholera if a single dose is found to be efficacious. A single-dose schedule could facilitate the inclusion of a global stockpile strategy.
The study design is a two-arm individually randomized double-blind placebo-controlled trial. The primary outcome of the study is the proportion of persons receiving 1 dose of vaccine or placebo who are detected with diarrhea with faecal excretion of V. cholera O1 in the study treatment centres from 7 days to 6 months after dosage and whose identity is confirmed through home visit.
详细描述
Background:
Cholera is a serious public health problem worldwide. Recently, unprecedented outbreaks have been seen in many countries including Zimbabwe, Haiti, Pakistan, Nepal, Guinea, Cuba, Congo, and Sierra Leone. These cholera outbreaks cause undue suffering with high mortality and morbidity figures as well as economic and social disruption. Bangladesh remains endemic for cholera, which peaks biannually with further increases seen during floods and cyclones .It affects all age groups, although the majority of fatal cases occur in children. Therefore, immunization against cholera remains an important public health tool for preventing and controlling the disease .
Considerable progress has been made during the last decade in the development of new generation oral vaccines against cholera. Dukoral , a killed whole cell V. cholerae O1 with recombinant B-subunit (rBS-WC), was the first to be licensed internationally and has been available mostly in developed countries as a traveller's vaccine. This vaccine is licensed in over 50 countries, including Bangladesh. The WHO now recommends Dukoral for both endemic and epidemic cholera. However, two disadvantages limit the broader use of Dukoral. First, its current price is high. Second, Dukoral needs to be administered with a buffer, which complicates large scale deployment.
The Shanchol vaccine is licensed in India and the vaccine was prequalified by the WHO in 2011.The technology for vaccine manufacturing has been transferred to Shantha Biotechnics in India (now owned by Sanofi) by IVI. A large double-blind placebo controlled phase III trial by NICED and IVI has evaluated the efficacy of the vaccine produced by Shantha in preventing diarrhea from cholera in 70,000 people in Kolkata. An analysis of the phase III trial after three years concluded that the vaccine was 66% efficacious . Advantages of the Shanchol™ vaccine include that its cost is lower and does not require administration with buffer, thus making it more feasible for use in mass vaccination programs in resource poor settings.
The current multi-dose schedules for both Dukoral and Shanchol™ have restricted the application of the oral cholera vaccine in situations where they are most needed. Getting a vaccine to the same people twice poses difficulties in the control of cholera in both endemic and epidemic settings. In a study performed in a cholera-endemic area in Kolkata, India it was found that Shanchol™ induces significant vibriocidal responses even after a single dose .This study is designed to determine the protective efficacy and duration of protection offered by a single dose regimen and is not intended to replace the recommended 2 dose regimen in endemic areas. This will be useful for epidemics and outbreaks situation.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy subjects > 1 year of age and above Living in high risk area for cholera Provision of Informed consent for participating in the study by participant /parent or guardian as well as verbal assent for children 11-17 years.
排除标准
- •Pregnant women Aged less than 1 year History of taking cholera vaccine
研究组 & 干预措施
Placebo
干预措施: Placebo (Biological)
Shanchol
干预措施: Shanchol (Biological)
结局指标
主要结局
Number of participants with a single dose regimen oral cholera vaccine Shanchol will get protection
时间窗: 7 days to 6 months
Shanchol vaccine will be given to healthy, non-pregnant residents aged one and above in Dhaka, Bangladesh, against culture-proven V. cholerae O1 diarrhea which has been detected in all treatment settings serving the catchment population.
次要结局
- Number of participants get protection with the single dose regimen of Shanchol against culture proven V. Cholerae O1 diarrhea with severe dehydration, V. Cholerae O139 diarrhea,V. Cholerae O139 diarrhea with severe dehydration .(7 days to 24 months)
- Number of participants with a single dose Shanchol with onset of 7 days to 6 months,7 days to 12 months, from 7 days to 18 months and 7 days to 24 months after dosing against acute watery diarrhoea detected in treatment centre(7 days to 24 months)
- Number of participants with a single dose Shanchol with onset of 7 days to 6 months,7 days to 12 months, from 7 days to 18 months and 7 days to 24 months after dosing against acute watery diarrhea with severe dehydration detected in treatment centre(7 days to 24 months)
- Number of participants get protection with a single dose Shanchol after dosing against culture-proven V. cholerae O1 diarrhea(7 days to 24 months)
- Serum vibriocidal antibody responses to oral cholera vaccine Shanchol in healthy,non-pregnant residents, aged one year and older in a subset of population(14 days)
- Safety up to 28 days following a single dose of the bivalent, killed, whole cell oral cholera vaccine Shanchol™ administered to healthy, non-pregnant residents one year and older(28 days)