Trial ChiCTR2100051998
Publication Cao Y, Cell Res, 2021

Funding: Mixed (Ministry of Science and Technology of China; Sinovac Biotech Ltd. provided CoronaVac vaccines; Longcom Biologic Pharmacy provided ZF2001 vaccines. )
Conflict of interest: no COI

Methods
RCT
Location : Single center / China
Follow-up duration (months): 0.5
CoronaVac booster n=41
ZF2001 booster n=81
Control n=42
Inclusion criteria
  • 1) Adult subjects (18 years old) having received two doses of inactivated COVID-19 vaccines between 4 and 8 months before the screening visit
  • 2) Subjects were in good health evaluated by investigators by inquiring case history and physical examination
  • 3) Female subjects of childbearing age have no lactation or pregnancy (negative urine pregnancy test) at the time of enrollment or no plan for family within the first 3 months after enrollment, take effective contraceptive measures within 2 weeks before enrollment
  • 4) Participants must provide consent indicating that he or she understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study and adhere to the procedures specified in the protocol.
Exclusion criteria
  • 1) Positive results for RT-qPCR tests of SARS-CoV-2
  • 2) Participant has clinical symptoms including fever, hoose, fatigue, stuffy nose, runny nose, sore throat, myalgia, diarrhea, shortness of breath, dyspnea, etc
  • 3) temperature ≥37.0ºC prior to vaccination. 4) Positive results for the urine pregnancy test
  • 5) Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to inactivated vaccine excipients
  • 6) Participant has a history of convulsions, epilepsy, encephalopathy or mental illness or family history
  • 7) Participant has illness including congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.
  • 8) Participant has severe liver and kidney disease and uncontrollable hypertension (systolic blood pressure >= 140 mmHg, diastolic blood pressure >= 90 mmHg), diabetes complications, malignant tumors, acute or chronic diseases
  • 9) Participant was diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, or other autoimmune diseases
  • 10) Participant was receiving anti-tuberculosis treatment
  • 11) Participant has known or suspected diseases including severe respiratory diseases, severe cardiovascular diseases, liver and kidney diseases, and malignant tumors
  • 12) Participant had a history of coagulation dysfunction (such as coagulation factor deficiency and coagulation diseases)
  • 13) Participant received immunotherapy or inhibitor treatment within 3 months before enrollment (continuous oral or infusion for more than 14 days)
  • 14) Participant received live attenuated vaccine within 1 month or other vaccines within 14 days before enrollment
  • 15) Participant received other study drugs within 3 months before enrollment
  • 16) Any condition or situation precluding or interfering the compliance with the protocol assessed by investigators.
Interventions
Intervention
1 IM booster dose of 3 mcg CoronaVac, 4-8 months after 2-dose CoronaVac schedule
1 IM booster dose of 25 mcg ZF2001, 4-8 months after 2-dose CoronaVac schedule
Control
No booster 4-8 months after 2-dose CoronaVac schedule
Participants
Randomized
164 participants
Characteristics of participants
Type of participants: Healthcare workers
N=164
47 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 0
Mean age:
Age range: NR
Description of participants
Healthcare professionals with no previous confirmed COVID-19 at a single center in China who had received two doses of CoronaVac in a 28-day interval 4–8 months earlier
Primary outcome
In the register
The incidence of effective immune reactivation on the 14th day of enrollment (Geometric mean titers (GMTs) of neutralizing antibodies produced in response to SARS-CoV-2 live virus increased 4 times or more from baseline, or changed from negative to positive from baseline)
In the report
Seroconversion rate on day 14 after the third dose of neutralizing antibodies to authentic SARS-CoV-2, which was defined as a change of titers from seronegative at baseline to seropositive, or a four-fold increase of titers for individuals whose titers were above seropositive cutoffs (1:8).
Documents
available

Protocol

NR

Statistical plan

*

Data-sharing stated: NR
Data accessibility: Correspondence to Yunlong Cao, Hongjie Yu, Xiaoliang Sunney Xie or Ronghua Jin. yunlongcao@pku.edu.cn yhj@fudan.edu.cn sunneyxie@biopic.pku.edu.cn ronghuajin@ccmu.edu.cn

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 registry and data supplement were used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan were available. The trial (n = 164) did not achieve its target sample size (n = 200). Only 2 arms (n=122) comparing CoronaVac booster dose (n=141) versus ZF2001 booster dose (n=181) were included in the analysis