MiscarriageNCT02499172
Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine (ShancholTM) in Nsanje Malawi
A study testing Shanchol in people with Miscarriage and Stillbirth, run by Johns Hopkins Bloomberg School of Public Health at 1 site in United States.
Trial summary
This study, to be carried out immediately following an emergency, reactive cholera vaccination campaign in Nsanje District, Malawi, will be a cohort study to estimate the safety of killed oral cholera vaccine (OCV), in pregnant women as measured by ShancholTM, on pregnancy outcomes and birth defects. Read more about this study
- Who is it for?
- Ages 15 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Miscarriage, Stillbirth, Cholera
- What is being tested?
- Shanchol
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,758 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to 30 Oct 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 to 49 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Women aged 15-49 years old at time of consent (all cohorts)
- Urine sample provided if pregnancy test required (Not required if experienced delivery outcome between March 30 and enrollment date, OR visibly pregnant AND has due date indicated in Health Passport) (all cohorts)
- Received at least one dose of OCV in 2015 (must be verified with OCV Vaccination Card) (Cohorts 1 \& 2)
- Estimated last menstruation at least 3 weeks before the first dose of OCV received (Nsanje) or before March 30, 2015 (Chikwawa) (Cohorts 1 \& 3)
- Estimated last menstruation at least 2 weeks after the final dose of OCV received (Nsanje) or after the last day of OCV Round 2 (Chikwawa) (Cohorts 2 \& 4)
- Residing in Nsanje or Chikwawa Districts since the first day of the vaccination campaign (30 March 2015) (Cohorts 2 \& 3)
- Provides informed consent (with additional consent by the parent or legal guardian for unmarried <18 years old) (All Cohorts)
Who cannot join
- Received at least one dose of OCV in 2015 (Cohorts 3 \& 4)
- An otherwise eligible pregnant women who is unable to be contacted after the second attempt within 48 hours after the first attempt to enroll (All cohorts)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, 21205
About this study
Official title: Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine
This study, to be carried out immediately following an emergency, reactive cholera vaccination campaign in Nsanje District, Malawi, will be a cohort study to estimate the safety of killed oral cholera vaccine (OCV), in pregnant women as measured by ShancholTM, on pregnancy outcomes and birth defects. While limited evidence which suggests that the vaccine is safe in pregnant women, this setting will allow investigators to answer this question in a community where more than 100,000 people will receive vaccine with no restrictions on pregnancy status. In past cholera vaccine campaigns including clinical trials, pregnant women were excluded due to lack of safety data. However, in this campaign, the decision by the Ministry of Health is that the benefits of offering vaccine to all individuals regardless of pregnancy status far outweigh any theoretical risk. Here the investigators specifically propose to:
Specific Objective 1: To conduct surveillance of pregnant women to detect adverse pregnancy outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in a reactive vaccination campaign that started on 30 March 2015. Through household surveying and enrollment of pregnant women with monthly follow-up visits, the investigators will determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and unvaccinated women in Nsanje and Chikwawa Districts, Malawi.
Read more
Specific Objective 2: To compare the cumulative incidence of pregnancy loss (miscarriage and stillbirth) of women who received oral cholera vaccine while they were pregnant to women who were vaccinated and became pregnant after the end of the final round of vaccination in Nsanje and Chikwawa Districts, Malawi.
Specific Objective 3: To compare the incidence of newborn malformations in a cohort of infants that had fetal exposure to oral cholera vaccine compared to those without such exposure in Nsanje and Chikwawa Districts, Malawi.
Read the detailed description
Although there are good reasons for women of reproductive age to participate in interventions that prevent cholera, cholera vaccination programs and studies have generally excluded pregnant women since there is little specific information on the safety of the vaccine during pregnancy. However, there are several biological reasons why inactivated OCVs are unlikely to have a harmful effect on fetal development. First, the bacteria in the vaccine are killed and do not replicate. Second, the vaccine antigens act locally on the gastrointestinal mucosa, are not absorbed, and do not enter the maternal or fetal circulation. Finally, the vaccines do not trigger systemic reactions (e.g., fever) associated with miscarriage in early pregnancy.According to the latest WHO position paper in relation to OCV, vaccination in countries where cholera is endemic may include groups that are particularly vulnerable to the severe forms of cholera, and for whom the vaccines are not contraindicated, such as pregnant women and HIV-infected individuals.
While the World Health Organization (WHO) recommends vaccination for pregnant women, the package inserts for Dukoral® and ShancholTM are more cautious and suggests that the vaccines are not recommended for use in pregnant women. Even so, the ShancholTM package insert states that, "Administration of ShancholTM to pregnant women may be considered after careful evaluation of the benefits and risks in case of a medical emergency or an epidemic". In the most recent results published in 2012, pregnant women inadvertently vaccinated with Dukoral® during the mass vaccination campaign in Zanzibar in 2009 did not experience any harmful effects. On the other hand, there is no information on the safety of ShancholTM vaccine in pregnant women. New evidence is needed to inform decisions on the true safety of this vaccine in pregnancy. If it is safe, this vaccine will be a valuable tool in reducing the burden of cholera in a population that disproportionately suffers from this disease.
On January 13, 2015, the President of the Republic of Malawi declared a state of disaster following the persistent rains that resulted in floods affecting 15 of the 28 districts in the country. The first confirmed case of cholera was reported in Malawi on February 11, 2015. As of 4 March 2015, Malawi had registered 72 cases with 2 deaths. To stop the outbreak of cholera, a cholera vaccination campaign program was carried out between 30 March 2015 and May 3 2015 targeting the camps and the nearby communities in Nsanje District. This campaign provided two doses of vaccine to all age eligible people irrespective of pregnancy status. This study is designed to do a follow-up of only the pregnant women aiming at the following objectives:
Specific Objective: To conduct surveillance of pregnant women to detect adverse pregnancy outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in a reactive vaccination campaign that started on 30 March 2015. Through household surveying and enrollment of pregnant women with monthly follow-up visits, the investigators will determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and unvaccinated women in Nsanje and Chikwawa Districts, Malawi.
- Conditions
- Miscarriage, Stillbirth, Cholera
- Being tested
- Shanchol
- Keywords
- Adverse pregnancy outcome
- Medical subject headings
- Abortion, Spontaneous, Stillbirth, Cholera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ShancholBiological
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1: Women who were pregnant and received at least one dose of ShancholTM during the mass OCV vaccination campaign. Receives: Biological: Shanchol |
| Cohort 2 | No intervention | Cohort 2: Women who received at least one dose and who became pregnant after the mass vaccination campaign; hence their fetuses were not exposed to the vaccine. |
| Cohort 3 | No intervention | Cohort 3: Women who were pregnant in Chikwawa District at the time of the vaccination campaign in Nsanje District, but who did not receive the vaccine during the campaign. |
| Cohort 4 | No intervention | Cohort 4: Women who become pregnant in Chikwawa District after the vaccination campaign in Nsanje District, and who did not receive the vaccine during the campaign. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Pregnancy Outcome
The primary analysis will compare adverse pregnancy outcome (miscarriage and stillbirth) in Cohorts 1 and 3.
Measured: Upto 42 weeks from the date of last menstrual period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study startJun 2015
- Primary completion30 Oct 2016
- Study completion30 Oct 2016
Why it stopped: Financial reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MiscarriageStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,758 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Malawi
- Responsible party
- Sponsor
- Investigators
- Mohammad Ali, PhD, Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499172
- Sponsor's protocol ID
- 00006369
- Status last verified
- Jan 2024
- First submitted
- 7 Jul 2015
- Last updated
- 3 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ali M, Nelson A, Luquero FJ, Azman AS, Debes AK, M'bang'ombe MM, Seyama L, Kachale E, Zuze K, Malichi D, Zulu F, Msyamboza KP, Kabuluzi S, Sack DA. Safety of a killed oral cholera vaccine (Shanchol) in pregnant women in Malawi: an observational cohort study. Lancet Infect Dis. 2017 May;17(5):538-544. doi: 10.1016/S1473-3099(16)30523-0. Epub 2017 Feb 2.
PubMed 28161570
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine
- ClinicalTrials.gov ID
- NCT02499172
- Acronym / sponsor ID
- 00006369
- Conditions
- Miscarriage, Stillbirth, Cholera
- Keywords
- Adverse pregnancy outcome
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Financial reason
- Enrolment
- 2,758 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- Ministry of Health, Malawi
- Study start
- Jun 2015
- Primary completion
- 30 Oct 2016 (actual)
- Study completion
- 30 Oct 2016 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study, to be carried out immediately following an emergency, reactive cholera vaccination campaign in Nsanje District, Malawi, will be a cohort study to estimate the safety of killed oral cholera vaccine (OCV), in pregnant women as measured by ShancholTM, on pregnancy outcomes and birth defects. While limited evidence which suggests that the vaccine is safe in pregnant women, this setting will allow investigators to answer this question in a community where more than 100,000 people will receive vaccine with no restrictions on pregnancy status. In past cholera vaccine campaigns including clinical trials, pregnant women were excluded due to lack of safety data. However, in this campaign, the decision by the Ministry of Health is that the benefits of offering vaccine to all individuals regardless of pregnancy status far outweigh any theoretical risk. Here the investigators specifically propose to:
Specific Objective 1: To conduct surveillance of pregnant women to detect adverse pregnancy outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in a reactive vaccination campaign that started on 30 March 2015. Through household surveying and enrollment of pregnant women with monthly follow-up visits, the investigators will determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and unvaccinated women in Nsanje and Chikwawa Districts, Malawi.
Specific Objective 2: To compare the cumulative incidence of pregnancy loss (miscarriage and stillbirth) of women who received oral cholera vaccine while they were pregnant to women who were vaccinated and became pregnant after the end of the final round of vaccination in Nsanje and Chikwawa Districts, Malawi.
Specific Objective 3: To compare the incidence of newborn malformations in a cohort of infants that had fetal exposure to oral cholera vaccine compared to those without such exposure in Nsanje and Chikwawa Districts, Malawi.
Detailed description
Although there are good reasons for women of reproductive age to participate in interventions that prevent cholera, cholera vaccination programs and studies have generally excluded pregnant women since there is little specific information on the safety of the vaccine during pregnancy. However, there are several biological reasons why inactivated OCVs are unlikely to have a harmful effect on fetal development. First, the bacteria in the vaccine are killed and do not replicate. Second, the vaccine antigens act locally on the gastrointestinal mucosa, are not absorbed, and do not enter the maternal or fetal circulation. Finally, the vaccines do not trigger systemic reactions (e.g., fever) associated with miscarriage in early pregnancy.According to the latest WHO position paper in relation to OCV, vaccination in countries where cholera is endemic may include groups that are particularly vulnerable to the severe forms of cholera, and for whom the vaccines are not contraindicated, such as pregnant women and HIV-infected individuals.
While the World Health Organization (WHO) recommends vaccination for pregnant women, the package inserts for Dukoral® and ShancholTM are more cautious and suggests that the vaccines are not recommended for use in pregnant women. Even so, the ShancholTM package insert states that, "Administration of ShancholTM to pregnant women may be considered after careful evaluation of the benefits and risks in case of a medical emergency or an epidemic". In the most recent results published in 2012, pregnant women inadvertently vaccinated with Dukoral® during the mass vaccination campaign in Zanzibar in 2009 did not experience any harmful effects. On the other hand, there is no information on the safety of ShancholTM vaccine in pregnant women. New evidence is needed to inform decisions on the true safety of this vaccine in pregnancy. If it is safe, this vaccine will be a valuable tool in reducing the burden of cholera in a population that disproportionately suffers from this disease.
On January 13, 2015, the President of the Republic of Malawi declared a state of disaster following the persistent rains that resulted in floods affecting 15 of the 28 districts in the country. The first confirmed case of cholera was reported in Malawi on February 11, 2015. As of 4 March 2015, Malawi had registered 72 cases with 2 deaths. To stop the outbreak of cholera, a cholera vaccination campaign program was carried out between 30 March 2015 and May 3 2015 targeting the camps and the nearby communities in Nsanje District. This campaign provided two doses of vaccine to all age eligible people irrespective of pregnancy status. This study is designed to do a follow-up of only the pregnant women aiming at the following objectives:
Specific Objective: To conduct surveillance of pregnant women to detect adverse pregnancy outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in a reactive vaccination campaign that started on 30 March 2015. Through household surveying and enrollment of pregnant women with monthly follow-up visits, the investigators will determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and unvaccinated women in Nsanje and Chikwawa Districts, Malawi.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: ShancholCohort 1: Women who were pregnant and received at least one dose of ShancholTM during the mass OCV vaccination campaign. |
| Cohort 2 | No intervention | –Cohort 2: Women who received at least one dose and who became pregnant after the mass vaccination campaign; hence their fetuses were not exposed to the vaccine. |
| Cohort 3 | No intervention | –Cohort 3: Women who were pregnant in Chikwawa District at the time of the vaccination campaign in Nsanje District, but who did not receive the vaccine during the campaign. |
| Cohort 4 | No intervention | –Cohort 4: Women who become pregnant in Chikwawa District after the vaccination campaign in Nsanje District, and who did not receive the vaccine during the campaign. |
Who may qualify
- Ages
- 15 to 49 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Women aged 15-49 years old at time of consent (all cohorts)
- Urine sample provided if pregnancy test required (Not required if experienced delivery outcome between March 30 and enrollment date, OR visibly pregnant AND has due date indicated in Health Passport) (all cohorts)
- Received at least one dose of OCV in 2015 (must be verified with OCV Vaccination Card) (Cohorts 1 \& 2)
- Estimated last menstruation at least 3 weeks before the first dose of OCV received (Nsanje) or before March 30, 2015 (Chikwawa) (Cohorts 1 \& 3)
- Estimated last menstruation at least 2 weeks after the final dose of OCV received (Nsanje) or after the last day of OCV Round 2 (Chikwawa) (Cohorts 2 \& 4)
Key exclusion criteria (2 listed)
- Received at least one dose of OCV in 2015 (Cohorts 3 \& 4)
- An otherwise eligible pregnant women who is unable to be contacted after the second attempt within 48 hours after the first attempt to enroll (All cohorts)
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 |
|---|---|---|
| Shanchol | Biological | Cohort 1 |
Primary outcome
Adverse Pregnancy Outcome
Time frame: Upto 42 weeks from the date of last menstrual period
The primary analysis will compare adverse pregnancy outcome (miscarriage and stillbirth) in Cohorts 1 and 3.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28161570Ali M, Nelson A, Luquero FJ, Azman AS, Debes AK, M'bang'ombe MM, Seyama L, Kachale E, Zuze K, Malichi D, Zulu F, Msyamboza KP, Kabuluzi S, Sack DA. Safety of a killed oral cholera vaccine (Shanchol) in pregnant women in Malawi: an observational cohort study. Lancet Infect Dis. 2017 May;17(5):538-544. doi: 10.1016/S1473-3099(16)30523-0. Epub 2017 Feb 2.
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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.
Mohammad Ali, PhD principal investigator
Johns Hopkins Bloomberg School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Shanchol in people with Miscarriage and Stillbirth, run by Johns Hopkins Bloomberg School of Public Health at 1 site in United States.
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 7 inclusion and 2 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: stopped early, as of the sponsor's last update on 3 Jan 2024. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Adverse Pregnancy Outcome (time frame: Upto 42 weeks from the date of last menstrual period). 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 NCT02499172, which also lists 1 linked publication.
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 3 Jan 2024.