Clinical trial NCT03582761: Efficacy Evaluation for Inactivated Vaccine (Vero Cell) Against EV71
Official title: A Phase IV Clinical Trial for Efficacy Evaluation for Inactivated Vaccine (Vero Cell) Against EV71: A Multicenter， Case-control Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hand, Foot and Mouth Disease
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: Wuhan Institute of Biological Products Co., Ltd
name: Hubei Provincial Center for Disease Control and Prevention
First posted: 2018-07-11
Enrollment: 40000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study is a multicenter, case-control phase IV clinical trial to evaluate the effectiveness of the EV71 vaccine. About 40000 children in the town aged 6-35 months will be recruited and vaccinated with EV71 vaccines, which account for 20-40% of the children aged 6-35 months in the areas. The subjects will be vaccinated with EV71 vaccine at day 0 and day 28. Other children of appropriate age in the town will choose voluntarily whether or not to be vaccinated with EV71 vaccine. All children's vaccination of EV71 vaccines will be recorded in the study areas and the coverage rate of EV71 vaccine in the town will be calculated. The vaccination is expected to complete before the epidemic peak of HFMD.

Surveillance of HFMD cases caused by EV71 will be conducted in hospitals of the study areas for 10-12 months, which cover a whole HFMD epidemic period. Throat and anal swabs will be collected from children with a clinically diagnosed HFMD for typing of human enteroviruses tested by PCR. The HFMD cases with EV71 positive will be recruited as cases, while those with EV71 negative will be recruited as test-negative controls. Besides, for each EV71-associated HFMD cases, the investigators will select 4 community controls mateced with each case for age, sex and residence.


Eligibility criteria: Inclusion Criteria:

For vaccination group：

* Healthy children aged 6-35 months
* Subjects who have been clinically judged to be healthy by the researcher after being asked about the medical history and related physical examination
* The subjects' guardians agree the requirements of the protocol and the relevant follow up visits
* The subjects' guardians agree and sign the informed consent

For case group：

* Aged from 6 to 47 months
* Clinical diagnosis of HFMD
* At least one throat swab or anal swab detected EV71 positive by PCR
* The subjects' guardians agree and sign the informed consent

For hospital control group：

* Aged from 6 to 47 months
* Clinical diagnosis of HFMD
* Throat swabs or anal swabs are positive for enterovirus and negative for EV71
* The subjects' guardians agree and sign the informed consent

For community control group：

* Aged from 6 to 47 months
* No clinically diagnosed HFMDs, and no fever, HFMD suspected symptoms, such as hand, foot and mouth herpes
* The same gender as the matched case
* The age is similar to that of matched case (for cases ≥ 12 months of age, the age difference is within ±3 months, for case \< 12 months of age, the age difference is within ±30 days)
* Near the residence of the case (the same village or adjacent village)
* The subjects' guardians agree and sign the informed consent

Exclusion Criteria:

For vaccination group：

* Subject who has a medical history of HFMD caused by EV71 or has been vaccinated with EV71 vaccine
* Subject who is known to be allegric to the componets of the vaccine
* Subject with fever or acute diseases or at acute stage of chronic diseases
* Subject with severe chronic diseases and allergies
* Subject with thrombocytopenia or hemorrhagic diseases
* Subject who is receiving immunosuppressive therapy or with immunodeficiency
* Subject with uncontrolled epilepsy and other progressive neurological illness, such as Guillain-Barre syndrome.

Exclusion Criteria for the second dose:

* Have severe allergic reaction after first dose
* Have severe adverse reactions related to first dose
* Any situation meet the exclusion criteria stated in the exclusion criteria for first dose
* Acute infection or illness
* Other factors that are not suitable for clinical trials according to the judgment of researchers For case group：
* Unknown of EV71 vaccination history
* EV71 related disease occurred within 28 days after the first vaccination
* The place of residence is not included in the study areas

For hospital control group：

* Unknown of EV71 vaccination history
* A history of HFMD caused by EV71 or unknown HFMD related pathogen
* The place of residence is not included in the study areas
* For community control group：
* For community control group：

For community control group：

* Unknown of EV71 vaccination history
* A history of HFMD caused by EV71 or unknown HFMD related pathogen

Primary outcomes:
measure: Odds ratio (OR) of the immunization of EV-A71 vaccine in cases vs control groups
timeFrame: within 12 months after completion of vaccination
Secondary outcomes:
measure: Incidence and severity of adverse reactions/adverse events in children aged 6-35 months after EV71 vaccine receiving.
timeFrame: 1 month after completion of vaccination
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Hubei Provincial Center for Diseases Control and Prevention
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Provincial Center for Diseases Control and Prevention
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Zhu Feng-Cai, Master
role: PRINCIPAL_INVESTIGATOR
References: