Trial NCT04582344
Publication Tanriover M, Lancet , 2021
Dates: 2020-09-15 to 2021-01-06
Funding: Public/non profit (Turkish Health Institutes Association (TUSEB))
Conflict of interest:
Methods | |
RCT | |
Location :
Multicenter / Turkey Follow-up duration (months): 6 | |
3 mcg CoronaVac (n=6650) Placebo (n=3568) |
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Inclusion criteria | 18-59 years of age; For only K1 cohort, health care workers such as medical doctor, nurse, ward boy, cleaner, hospital technician, administrative personnel who work in any department of a healthcare unit; Signed informed consent |
Exclusion criteria | Previously PCR positive for COVID-19; IgG or IgM is positive; 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; Known allergy to components of the study vaccine or control; Use of immunosuppressant therapy regimens within the six months prior to enrollment in the study or 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; History of asplenia; 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 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; Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate; 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; Received live attenuated virus vaccine 14 days prior to enrollment in the study; Inactivated vaccine or sub unit vaccine 7 days prior to enrollment in the study; Fever (oral temperature >37.2℃, axillary temperature will not be accepted) within the past 24 hours; 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; Any confirmed or suspected autoimmune disease or immunodeficiency disease, including human immunodeficiency virus (HIV) infection |
Interventions | |
Intervention
2 IM doses of 3mcg, 14 days apart |
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Control
2 IM doses of 0.45 mg/mL aluminium, 14 days apart | |
Participants | |
Randomized 10218 participants | |
Characteristics of participants Type of participants: Adults, Healthcare workers N=10218 5907 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR | |
Description of participants Healthy healthcare workers and adults aged 18–59 years with no history of COVID-19 from 24 centres in Turkey | |
Primary outcome | |
In the register Protection Indexes of Two Vaccine Doses For Symptomatic COVID-19 [ Time Frame: 2 weeks afterthe second dose of vaccination ] | |
In the report Symptomatic COVID-19 cases confirmed by RT-PCR at least 14 days after the second dose of vaccination, assessed in the per protocol population | |
Variants description | |
Variants | |
Description * | |
Documents avalaible |
Protocol Yes. In English Statistical plan * Data-sharing stated:
Yes, upon completion of the clinical trial and publication of the completed study results |
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 supplementary materials, study registry and protocol were used in data extraction and risk of bias assessment. An interim analysis (data lock date: March 16, 2021) was presented and the study was terminated due an emergency use authorization for CoronaVac on Jan 13, 2021. As a result, the estimated enrollment specified in the registry was not achieved (n=13000), some outcomes were not reported in the paper, and some outcomes were reported at an earlier follow-up point than pre-specified in the registry. Participants were recruited in two consecutive cohorts of healthcare workers and general population. There is no change from the trial registration in the intervention and control arms. Quote: "During the study, the Ministry of Health gave an emergency use authorisation for CoronaVac on Jan 13, 2021, and started an immediate vaccination programme initially for health-care workers and later for the public, prioritising older adults (aged ≥65 years). Although recruitment of volunteers was ongoing at this time, to comply with the principles of the Declaration of Helsinki regarding using a placebo for human subjects in medical research, the ethics committee suggested discontinuing the masking and injection of participants in the placebo group. Consequently, the placebo recipients were offered vaccines, first in K1 and later in K2." |