Randomized Controlled Trial of Killed Oral Cholera Vaccine in Kolkata

Study Overview
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Brief Summary
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The primary purpose of this study is to estimate the efficacy of a two-dose regimen of the oral killed bivalent cholera vaccine when administered to individual residing in a cholera-endemic area in India.

Detailed Description
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Cholera remains a serious public health problem worldwide. Provision of safe water and food, establishment of adequate sanitation, and implementation of personal and community hygiene constitute the main public health interventions against cholera. These measures cannot be implemented fully in the near future in most cholera-endemic areas. A safe, effective, and affordable vaccine would be a useful tool for cholera prevention and control.The World Health Organization recently recommended that the newer generation cholera vaccines be considered in certain endemic and epidemic situations, but indicated that demonstration projects are needed to provide more information about the costs, feasibility, and impact of using these vaccines. Starting in the mid-1980s, following technology transfer from Prof Jan Holmgren in Sweden, Vietnamese scientists at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi developed and produced an oral, killed cholera vaccine for the country's public health programs (10). Since licensure of the oral cholera vaccine in Vietnam, more than 5 million doses have been administered without any report of serious adverse events. The vaccine is produced according to recommended WHO guidelines (6) at the NIHE's newly privatized arm, the Company for Vaccine and Biological Production No. 1 (VABIOTECH) in Hanoi. Recently the vaccine was reformulated in order to comply with WHO standards to further internationalize this vaccine. Phase II trials of this reformulated vaccine have been performed among 148 adults in SonLa,Vietnam (18) and among 100 adults and 100 children in Kolkata, India. Results from these trials reveal that the vaccine is safe and immunogenic. A double-blind randomised phase III trial of the reformulated oral killed bivalent cholera vaccine in an urban slum site in Kolkata is proposed by the National Institute of Cholera and Enteric Diseases (NICED) in collaboration with the International Vaccine Institute (IVI). The IVI has negotiated an agreement between VABIOTECH and Shantha Biotechnics PVT LTD for the vaccine and placebo to be used during the trial. VABIOTECH will produce bulk oral killed bivalent cholera vaccine under quality control conditions to be supervised by IVI staff. Shanta will purchase bulk vaccine from VABIOTECH, fill and finish the bulk vaccine, and obtain regulatory clearance for use of the vaccine in the phase III trial. Shanta will purchase the bulk placebo agent for use in the trial from IVAC (also in Vietnam) and Shanta will fill and finish the placebo and obtain regulatory clearance for use of the placebo in the phase III trial. Shanta will later obtain the technology for future production of the oral killed bivalent cholera vaccine. The results of this trial will pave the way for the use of this vaccine in India and other cholera-endemic areas.

Official Title
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A Randomized Controlled Trial of the Bivalent Killed Whole Cell Oral Cholera Vaccine in Eastern Kolkata, West Bengal, India

Conditions
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Diarrhea, Cholera, Vibrio Infections

Intervention / Treatment
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* Biological: bivalent killed whole cell oral cholera vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All healthy, consenting, non-pregnant (as ascertained by history) residents at least 1 year of age of the study area Exclusion Criteria: individuals who are too weak to get out of bed to receive the vaccine; pregnant women (identified through verbal screening); and those less than 1 year of age

Ages Eligible for Study
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Minimum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Cholera Vaccine | Biological: bivalent killed whole cell oral cholera vaccine<br>* Given as 1.5 mL dose, given orally in 2 doses 14 days apart, each dose contains: V. cholerae O1 Inaba El Tor strain Phil 6973 formalin killed 600 Elisa units (EU) LPS V. cholerae O1 Ogawa classical strain Cairo 50 heat killed 300 EU LPS V. cholerae O1 Ogawa classical strain Cairo 50 formalin killed 300 EU LPS V. cholerae O1 Inaba classical strain Cairo 48 heat killed 300 EU LPS V. cholerae O139 strain 4260B formalin killed 600 EU LPS<br>|
| Placebo Comparator: 2<br>Placebo | Biological: Placebo<br>* Heat Killed E. coli K12 in an optical turbidity identical to killed oral cholera vaccine, in 1.5 mL oral dose given twice, at least 14 days apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| culture-proven V. cholerae O1 diarrhoea episodes severe enough to require treatment in a health care facility. |  | 1095 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Episodes of acute watery diarrhoea severe enough to require treatment in a health care facility |  | 1095 days | 
| Serum vibriocidal responses, compared to baseline |  | 14 days and 365 days after second dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bivalent killed whole cell oral cholera vaccine, double blind randomized clinical trial