Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02499172 |
| Other study ID # |
00006369 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 2015 |
| Est. completion date |
October 30, 2016 |
Study information
| Verified date |
January 2024 |
| Source |
Johns Hopkins Bloomberg School of Public Health |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
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.
