Randomized Controlled Trial of Killed Oral Cholera Vaccine in Kolkata
Randomized Controlled Trial of Killed Oral Cholera Vaccine in Kolkata
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.
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.
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