Covid-19 Living Data

Trial NCT04651790
Publication Bueno S, Clin Infect Dis, 2021
Dates: 2020-11-27 to 2021-02-10
Funding: Public/non profit (Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Chile Follow-up duration (months): 1.4
	• CoronoVac (3 mcg) (n=270) • Placebo (aluminum hydroxide adjuvant) (n=164)
Inclusion criteria	Healthcare workers who were in contact with possible or confirmed cases of COVID-19 ≥18 years old.
Exclusion criteria	History of confirmed symptomatic SARS-CoV-2 infection Pregnancy Allergy to vaccine components Immunocompromised conditions Uncontrolled neurological, cardiac, pulmonary, hepatic, or renal disease, according to anamnesis or physical examination Behavioral, cognitive, or psychiatric illness that, in the opinion of the principal investigator or his medical representative, affects the participant's ability to understand and collaborate with the requirements of the study protocol Use of immunosuppressive therapies six months before inclusion in the study or its scheduled use within two years of inclusion Have received an immunosuppressive dose of corticosteroids in the last three months before inclusion in the study or scheduled administration of an immunosuppressive dose of corticosteroids for the three months following inclusion in the study History of asplenia, either anatomic or functional History of bleeding disorders Any alcohol or drug abuse in the last 12 months before inclusion in the study that has caused medical, professional, or family problems, as indicated by clinical history Have received blood products (transfusions or immunoglobulins) in the last three months before inclusion in the study Have received any vaccine with a live attenuated virus in the last 28 days or inactivated vaccine in the last 14 days before their inclusion in the study, or have immunization scheduled for the first 28 days after their inclusion in the study Participation in another clinical trial with product administration under investigation during the six months before its inclusion in the study or scheduled participation in another clinical trial in the two years following inclusion Previous participation in a COVID-19 vaccine evaluation study or previous exposure to a COVID-19 vaccine Fever (>37.8°C) within 72 hours before vaccination Any other condition that, in the opinion of the principal investigator or his medical representative, could jeopardize the safety or rights of a potential participant or that would prevent him from complying with this protocol.
Interventions
	Intervention 2 IM doses of 3 mcg CoronaVac, 14 days apart
	Control 2 IM doses of adjuvant, 14 days apart
Participants
	Randomized 434 participants
	Characteristics of participants Type of participants: People in close contact with COVID-19 patients, Healthcare workers. N=434 166 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: NR
	Description of participants Adult healthcare workers with no history of confirmed symptomatic SARS-CoV-2 infection who were in contact with possible or confirmed cases of COVID-19 in 8 sites in Chile.
Primary outcome
	In the register Frequency of solicited and unsolicited adverse events that occur during the period of one week after each dose of the vaccine in two vaccination schedules: 0,14 and 0,28 days stratified by age group (18-59 years, and 60 or more years). [ Time Frame: During the first 7 days after each dose of vaccine ] Incidence of symptomatic cases of virologically confirmed COVID-19 two weeks after the second dose of each vaccination schedule. [ Time Frame: Two weeks after second dose up to one year after first dose ]
	In the report The primary aim was to evaluate the frequency of solicited and unsolicited AEs that occur during 7 days after each dose, stratified by age group (aged 18-59 and ≥60).
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes Data accessibility: All the data included in the manuscript is available upon request to the corresponding authors: Alexis M Kalergis and Susan M Bueno akalergis@bio.puc.cl, sbueno@bio.puc.cl.
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, the trial registry, protocol and statistical plan were used in data extraction and assessment of risk of bias. The article reports an interim analysis including 434 participants. As this is an interim analysis, the pre-stated sample size was not achieved. Substantial changes were made to the original trial registry regarding participant characteristics (changed to no longer being restricted to health care workers), the intervention comparison (vaccine versus placebo control replaced with vaccine delivered days 0 and 28 versus days 0 and 14), blinding (changed from blinded to open label) and outcomes (removal of two secondary outcomes). However, the interim analysis reported in the pre-print adheres to the original trial registry. In the article, authors report randomization with 1:1 ratio for intervention/control groups however, the number of participants per group on the flow chart and result tables, doesn't correspond to this ratio. This trial was updated on October 11th 2021, after the publication of the study report.