Clinical trial NCT04747821: An Effectiveness Study of the Sinovac's Adsorbed COVID-19 (Inactivated) Vaccine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Covid19
Keywords: COVID-19 Vaccines
Vaccines, Inactivated
Lead sponsor: Butantan Institute
Sponsor class: OTHER_GOV
First posted: 2021-02-10
Enrollment: 27711
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Groups of cluster are allocated to offer vaccination in a stepped-wedge mode.
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Adults 18 years of age or older;
2. Resident in the study area;
3. Show voluntary intention to participate in the study, documented by the informed consent form signed by participant.

Exclusion Criteria:

1. 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;
2. 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;
3. 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;
4. 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;
5. 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;
6. History of severe allergic reactions or anaphylaxis to the study vaccine or to components thereof;
7. History of asplenia;
8. 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;
9. Previous participation in a study to evaluate a COVID-19 vaccine or prior exposure to a COVID-19 vaccine;
10. 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.
11. 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;
12. 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;
13. 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);
14. 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);
15. 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;
16. 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
17. 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.

Primary outcomes:
measure: Incidence of COVID-19 cases after two-doses immunization schedule in clusters in the first quarter of study
timeFrame: Thirteen weeks after the beginning of study vaccination
Secondary outcomes:
measure: Incidence of COVID-19 cases after two-doses immunization schedule in clusters up to one year of study
timeFrame: One year after the beginning of study vaccination
measure: Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to immunization status
timeFrame: One year after the beginning of study vaccination
measure: Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to pre-existing SARS-CoV-2 antibodies
timeFrame: One year after the beginning of study vaccination
measure: Incidence of COVID-19 cases after two-doses immunization schedule in clusters according to immunization coverage
timeFrame: One year after the beginning of study vaccination
measure: Incidence of hospitalization and death due to COVID-19 after two-doses immunization schedule in clusters
timeFrame: One year after the beginning of study vaccination
measure: Change in average number of reported COVID-19 cases in the study area in comparison to other neighboring cities
timeFrame: One year after the beginning of study vaccination
measure: Medically-attended adverse reactions to the study vaccine
timeFrame: One week after each vaccination
measure: Frequency of severe COVID-19 cases
timeFrame: From first vaccination up to one year after first dose
measure: Frequency of adverse events of special interest after immunization
timeFrame: From first vaccination up to one year after first dose
measure: Acceptability of the study vaccine
timeFrame: Two weeks after the beginning of study vaccination of the corresponding cluster
measure: Adherence to vaccination schedule
timeFrame: Six weeks after the beginning of study vaccination of the corresponding cluster
Other outcomes:
measure: Frequency of SARS-CoV-2 variants in the study area
timeFrame: One year after the beginning of study vaccination
Locations:
city: Serrana
country: Brazil
facility: Hospital Estadual de Serrana
state: SP
Study officials:
affiliation: Butantan Institute
name: Fernanda Boulos, MD, MSc
role: STUDY_DIRECTOR
References: