An Effectiveness Study of the Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine

Study Overview
=================
Brief Summary
-----------------
This is a stepped-wedge cluster randomized trial to assess effectiveness of Sinovac's Adsorbed COVID-19 (Inactivated) vaccine. Residents in the urban area of a municipality are eligible to participate. The city was divided in clusters and those cluster were grouped to determine the offer of vaccination in four steps. The vaccine will be offered to adults (18 years old and above) according to the location of their homes in a cluster. The vaccine schedule is two doses with four-weeks interval. Baseline samples to determine previous immunity will be collected before vaccination. Cases of COVID-19 reported in the city will be recorded according to the WHO clinical progression scale. Comparison of periods before and after vaccination and relation to immunization coverage will be considered for the assessment of effectiveness in the clusters and groups of clusters.

Official Title
-----------------
A Stepped-wedge Cluster Randomized Trial to Assess the Effectiveness of the Use of the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: Adsorbed COVID-19 (Inactivated) Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 years of age or older; Resident in the study area; Show voluntary intention to participate in the study, documented by the informed consent form signed by participant. Exclusion Criteria: For females: Pregnancy (confirmed by positive beta-hCG test), breastfeeding or intent to engage in sexual relations with reproductive intent without use of birth control methods in the three months following vaccination; Evidence of uncontrolled neurological, cardiac, pulmonary, hepatic or renal disease, according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease; Diseases with impaired immune system including: neoplasms (except basal cell carcinoma), congenital or acquired immunodeficiencies and autoimmune diseases not controlled according to anamnesis or physical examination. Significant changes in treatment or hospitalizations due to worsening of the condition in the last three months are indicators of uncontrolled disease; Behavioral, cognitive or psychiatric disease that, in the opinion of the principal investigator or his or her representative physician, affects the participant's ability to understand and cooperate with all study protocol requirements; Any alcohol or drug abuse over the 12 months prior to enrollment in the study that has caused medical, professional or family problems, indicated by clinical history; History of severe allergic reactions or anaphylaxis to the study vaccine or to components thereof; History of asplenia; Participation in another clinical trial with an investigational product in the six months prior to enrollment in the study or planned participation in another clinical trial within the two years following enrollment; Previous participation in a study to evaluate a COVID-19 vaccine or prior exposure to a COVID-19 vaccine; Use of immunosuppressant therapy regimens within the six months prior to enrollment in the study for planned use within the two years following enrollment. Immunosuppressant therapy regimens include: antineoplastic chemotherapy, radiation therapy and immunosuppressants to induce transplant tolerance, among others. Use of immunosuppressive doses of corticosteroids within the three months prior to the enrollment in the study and planned use of immunosuppressive doses of corticoids within the three months following enrollment in the study. Immunosuppressive doses of corticosteroids will be considered the equivalent prednisone 20 mg/day for adults, for longer than one week. Continued use of topical or nasal corticosteroids is not considered an immunosuppressant; Received blood products (transfusions or immunoglobulins) within the three months prior to enrollment in the study, or planned administration of blood products or immunoglobulins within the two years following enrollment in the study; Suspected or confirmed fever within the 72 hours prior to vaccination or axillary temperature greater than 37.8 °C* on the day of vaccination (enrollment may be postponed until participant has gone 72 hours without fever); Possible or confirmed case of COVID-19 on the day of vaccination (vaccination can be postponed until the participant completes 72 hours without symptoms or the diagnosis is ruled out); Received live attenuated virus vaccine or inactivated vaccine within the 28 days or 14 days, respectively, prior to enrollment in the study, or immunization planned within the 28 days after enrollment in the study; History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture Any other condition that, in the opinion of the principal investigator or his/her representative physician, could put the safety/rights of potential participants at risk or prevent them from complying with this protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Groups of cluster are allocated to offer vaccination in a stepped-wedge mode.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First group of clusters<br>Adsorbed COVID-19 (Inactivated) vaccine offered in the first week of study The vaccine is administrated in two doses with a four-weeks interval | Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br>* Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac<br>* Other names: CoronaVac;|
| Experimental: Second group of clusters<br>Adsorbed COVID-19 (Inactivated) vaccine offered in the second week of study The vaccine is administrated in two doses with a four-weeks interval | Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br>* Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac<br>* Other names: CoronaVac;|
| Experimental: Third group of clusters<br>Adsorbed COVID-19 (Inactivated) vaccine offered in the third week of study The vaccine is administrated in two doses with a four-weeks interval | Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br>* Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac<br>* Other names: CoronaVac;|
| Experimental: Fourth group of clusters<br>Adsorbed COVID-19 (Inactivated) vaccine offered in the fourth week of study The vaccine is administrated in two doses with a four-weeks interval | Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br>* Adsorbed COVID-19 (inactivated) Vaccine manufactured by Sinovac<br>* Other names: CoronaVac;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of COVID-19 cases after two-doses immunization schedule in clusters in the first quarter of study | Number of virologically-confirmed symptomatic COVID-19 six weeks after beginning of study vaccination up to thirteen weeks | Thirteen weeks after the beginning of study vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of COVID-19 cases after two-doses immunization schedule in clusters up to one year of study | Number of virologically-confirmed symptomatic COVID-19 six weeks after beginning of study vaccination up to one year | One year after the beginning of study vaccination | 
| Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to immunization status | Number of virologically-confirmed symptomatic COVID-19 six weeks after beginning of study vaccination up to one year according to immunization status | One year after the beginning of study vaccination | 
| Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to pre-existing SARS-CoV-2 antibodies | Number of virologically-confirmed symptomatic COVID-19 six weeks after beginning of study vaccination up to one year according to pre-existing SARS-CoV-2 antibodies | One year after the beginning of study vaccination | 
| Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to immunization coverage | Number of virologically-confirmed symptomatic COVID-19 six weeks after beginning of study vaccination up to one year according to immunization coverage | One year after the beginning of study vaccination | 
| Incidence of hospitalization and death due to COVID-19 after two-doses immunization schedule in clusters | Number of hospitalization and death due to COVID-19 six weeks after beginning of study vaccination up to one year | One year after the beginning of study vaccination | 
| Change in average number of reported COVID-19 cases in the study area in comparison to other neighboring cities | Average number of reported COVID-19 cases in the microregion where the study area is located | One year after the beginning of study vaccination | 
| Medically-attended adverse reactions to the study vaccine | Number of medically-attended adverse reactions to the study vaccine | One week after each vaccination | 
| Frequency of severe COVID-19 cases | Frequency of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine | From first vaccination up to one year after first dose | 
| Frequency of adverse events of special interest after immunization | Frequency of adverse events of special interest after receiving, at least, one dose of the vaccine | From first vaccination up to one year after first dose | 
| Acceptability of the study vaccine | Acceptability rate of the study vaccine in the eligible population of each cluster | Two weeks after the beginning of study vaccination of the corresponding cluster | 
| Adherence to vaccination schedule | Adherence rate to vaccination schedule in the population of each cluster | Six weeks after the beginning of study vaccination of the corresponding cluster | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19 Vaccines, Vaccines, Inactivated