DiarrheaPhase 3NCT00289224
Randomized Controlled Trial of Killed Oral Cholera Vaccine in Kolkata
A Phase 3 study testing bivalent killed whole cell oral cholera vaccine in people with Diarrhea and Cholera, run by International Vaccine Institute at 1 site in India.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 months and olderHealthy volunteers can take part
- Conditions the study is for
- Diarrhea, Cholera, Vibrio Infections
- What is being tested?
- bivalent killed whole cell oral cholera vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69,329 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2006to May 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- All healthy, consenting, non-pregnant (as ascertained by history) residents at least 1 year of age of the study area
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
National Institute of Cholera and Enteric Diseases
Kolkata, West Bengal
About this study
Official title: A Randomized Controlled Trial of the Bivalent Killed Whole Cell Oral Cholera Vaccine in Eastern Kolkata, West Bengal, India
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.
Read the detailed description
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.
- Conditions
- Diarrhea, Cholera, Vibrio Infections
- Being tested
- bivalent killed whole cell oral cholera vaccine, Placebo
- Keywords
- bivalent killed whole cell oral cholera vaccine, double blind randomized clinical trial
- Medical subject headings
- Diarrhea, Cholera, Vibrio Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bivalent killed whole cell oral cholera vaccineBiological
Given as 1.5 mL dose, given orally in 2 doses 14 days apart, each dose contains:
- 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
PlaceboBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Cholera Vaccine Receives: Biological: bivalent killed whole cell oral cholera vaccine |
| 2 | Placebo comparator | Placebo Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
culture-proven V. cholerae O1 diarrhoea episodes severe enough to require treatment in a health care facility.
Measured: 1095 days
Secondary outcomes (2)
Episodes of acute watery diarrhoea severe enough to require treatment in a health care facility
Measured: 1095 days
Serum vibriocidal responses, compared to baseline
Measured: 14 days and 365 days after second dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2006 (estimated)
- Study startJul 2006
- Primary completionDec 2011
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69,329 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Vaccine Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited
- Responsible party
- Sponsor
- Investigators
- Dipika Sur, MD, Principal investigator, National Institute of Cholera and Enteric Diseases, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00289224
- Sponsor's protocol ID
- C8phIII
- Status last verified
- Mar 2012
- First submitted
- 7 Feb 2006
- Last updated
- 31 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Rao R, Nguyen TV, Donner A, Ganguly NK, Nair GB, Bhattacharya SK, Clemens JD. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009 Nov 14;374(9702):1694-702. doi: 10.1016/S0140-6736(09)61297-6. Epub 2009 Oct 8.
PubMed 19819004Islam MT, Im J, Ahmmed F, Kim DR, Tadesse BT, Kang S, Khanam F, Chowdhury F, Ahmed T, Firoj MG, Aziz AB, Hoque M, Park J, Jeon HJ, Kanungo S, Dutta S, Zaman K, Khan AI, Marks F, Kim JH, Qadri F, Clemens JD. Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India. Open Forum Infect Dis. 2023 Nov 21;10(11):ofad535. doi: 10.1093/ofid/ofad535. eCollection 2023 Nov.
PubMed 38023545Fong Y, Halloran ME, Park JK, Marks F, Clemens JD, Chao DL. Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial. BMC Infect Dis. 2018 Feb 20;18(1):84. doi: 10.1186/s12879-018-2981-4.
PubMed 29463233Ali M, Debes AK, Luquero FJ, Kim DR, Park JY, Digilio L, Manna B, Kanungo S, Dutta S, Sur D, Bhattacharya SK, Sack DA. Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial. PLoS Med. 2016 Sep 13;13(9):e1002120. doi: 10.1371/journal.pmed.1002120. eCollection 2016 Sep.
PubMed 27622507Ali M, Sur D, You YA, Kanungo S, Sah B, Manna B, Puri M, Wierzba TF, Donner A, Nair GB, Bhattacharya SK, Dhingra MS, Deen JL, Lopez AL, Clemens J. Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India. Clin Infect Dis. 2013 Apr;56(8):1123-31. doi: 10.1093/cid/cit009. Epub 2013 Jan 29.
PubMed 23362293Sur D, Kanungo S, Sah B, Manna B, Ali M, Paisley AM, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Rao R, Nguyen TV, Han SH, Attridge S, Donner A, Ganguly NK, Bhattacharya SK, Nair GB, Clemens JD, Lopez AL. Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial. PLoS Negl Trop Dis. 2011 Oct;5(10):e1289. doi: 10.1371/journal.pntd.0001289. Epub 2011 Oct 18.
PubMed 22028938
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of the Bivalent Killed Whole Cell Oral Cholera Vaccine in Eastern Kolkata, West Bengal, India
- ClinicalTrials.gov ID
- NCT00289224
- Acronym / sponsor ID
- C8phIII
- Conditions
- Diarrhea, Cholera, Vibrio Infections
- Keywords
- bivalent killed whole cell oral cholera vaccine, double blind randomized clinical trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69,329 participants (actual)
- Lead sponsor
- International Vaccine InstituteUniversity, hospital or other
- Collaborators
- National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited
- Study start
- Jul 2006
- Primary completion
- Dec 2011 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 9 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: bivalent killed whole cell oral cholera vaccineCholera Vaccine |
| 2 | Placebo comparator | Biological: PlaceboPlacebo |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All healthy, consenting, non-pregnant (as ascertained by history) residents at least 1 year of age of the study area
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bivalent killed whole cell oral cholera vaccineGiven 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 | Biological | 1 |
| PlaceboHeat 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. | Biological | 2 |
Primary outcome
culture-proven V. cholerae O1 diarrhoea episodes severe enough to require treatment in a health care facility.
Time frame: 1095 days
2 secondary outcomes
Episodes of acute watery diarrhoea severe enough to require treatment in a health care facility
Time frame: 1095 days
Serum vibriocidal responses, compared to baseline
Time frame: 14 days and 365 days after second dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2014.
- Results publication: PubMed 19819004Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Rao R, Nguyen TV, Donner A, Ganguly NK, Nair GB, Bhattacharya SK, Clemens JD. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009 Nov 14;374(9702):1694-702. doi: 10.1016/S0140-6736(09)61297-6. Epub 2009 Oct 8.
- Derived from this study: PubMed 38023545Islam MT, Im J, Ahmmed F, Kim DR, Tadesse BT, Kang S, Khanam F, Chowdhury F, Ahmed T, Firoj MG, Aziz AB, Hoque M, Park J, Jeon HJ, Kanungo S, Dutta S, Zaman K, Khan AI, Marks F, Kim JH, Qadri F, Clemens JD. Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India. Open Forum Infect Dis. 2023 Nov 21;10(11):ofad535. doi: 10.1093/ofid/ofad535. eCollection 2023 Nov.
- Derived from this study: PubMed 29463233Fong Y, Halloran ME, Park JK, Marks F, Clemens JD, Chao DL. Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial. BMC Infect Dis. 2018 Feb 20;18(1):84. doi: 10.1186/s12879-018-2981-4.
- Derived from this study: PubMed 27622507Ali M, Debes AK, Luquero FJ, Kim DR, Park JY, Digilio L, Manna B, Kanungo S, Dutta S, Sur D, Bhattacharya SK, Sack DA. Potential for Controlling Cholera Using a Ring Vaccination Strategy: Re-analysis of Data from a Cluster-Randomized Clinical Trial. PLoS Med. 2016 Sep 13;13(9):e1002120. doi: 10.1371/journal.pmed.1002120. eCollection 2016 Sep.
- Derived from this study: PubMed 23362293Ali M, Sur D, You YA, Kanungo S, Sah B, Manna B, Puri M, Wierzba TF, Donner A, Nair GB, Bhattacharya SK, Dhingra MS, Deen JL, Lopez AL, Clemens J. Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India. Clin Infect Dis. 2013 Apr;56(8):1123-31. doi: 10.1093/cid/cit009. Epub 2013 Jan 29.
- Derived from this study: PubMed 22028938Sur D, Kanungo S, Sah B, Manna B, Ali M, Paisley AM, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Rao R, Nguyen TV, Han SH, Attridge S, Donner A, Ganguly NK, Bhattacharya SK, Nair GB, Clemens JD, Lopez AL. Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial. PLoS Negl Trop Dis. 2011 Oct;5(10):e1289. doi: 10.1371/journal.pntd.0001289. Epub 2011 Oct 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dipika Sur, MD principal investigator
National Institute of Cholera and Enteric Diseases, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bivalent killed whole cell oral cholera vaccine in people with Diarrhea and Cholera, run by International Vaccine Institute at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
culture-proven V. cholerae O1 diarrhoea episodes severe enough to require treatment in a health care facility. (time frame: 1095 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00289224, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2014.