Trial RBR–9nn3scw
Publication Costa Clemens SA, Lancet, 2022
Dates: 2021-08-16 to 2021-09-01
Funding: Mixed (Ministério da Saúde - Brasil (Ministry of Health, Brazil); support from AstraZeneca for serological assays)
Conflict of interest: Yes

Methods
RCT
Location : Multicenter / Brazil
Follow-up duration (months): 1
Ad26.COV2-S heterologous booster (n = 306)
BNT162b2 heterologous booster (n = 340)
ChAdOx1 heterologous booster (n = 304)
CoronaVac homologous booster (n = 290)
Inclusion criteria
  • 18 years or older
  • had received their second doses of CoronaVac 182 days (plus or minus 30 days) before enrolment
  • female participants were not pregnant, puerperal, or nursing
  • and all participants had given written informed consent
Exclusion criteria
  • History of laboratory-confirmed COVID-19 (or with fever or acute disease within 3 days before randomisation)
  • serious vaccine-related adverse reactions
  • known bleeding disorders, neurological disorders, or history of Guillain-Barré syndrome
  • people with autoimmune disease (excluding people with Hashimoto’s thyroiditis, vitiligo, psoriasis, lupus discords, HIV positive, or on HIV treatment)
  • people on immunosuppressive medications within 15 days of vaccine
  • receipt of other investigational products, other vaccines within 14 days of enrolment or plans to receive vaccine within 28 days of vaccination, monoclonals within 9 months of day 1 or planned during the study, intravenous immunoglobulin, or other blood products
  • and any condition that could interfere with the primary objectives or represent additional risk to participants
Interventions
Intervention
1 IM booster dose of 5×10¹⁰ vp ChAdOx1, 152-210 days after primary CoronaVac schedule
1 IM booster dose of 30 mcg BNT162b2, 152-210 days after primary CoronaVac schedule
1 IM booster dose of 5×10¹⁰ vp AD26.COV2-S, 152-210 days after primary CoronaVac schedule
Control
1 IM booster dose of 600 SU CoronaVac, 152-210 days after primary CoronaVac schedule
Participants
Randomized
1240 participants
Characteristics of participants
Type of participants: Healthy adults
N=1240
476 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 3
Mean age:
Age range: 21-96
Description of participants
Healthy adults with no history of confirmed covid-19 who had previously received 2 doses of CoronaVac at two centers in Brazil
Primary outcome
In the register
Humoral immune response to a homologous or heterologous (3rd dose) booster regimen in individuals previously vaccinated with two doses of Sinovac/Butantan
In the report
Non-inferiority of anti-spike IgG antibodies 28 days after the booster dose
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated: Yes
Data accessibility: Data are provided as a CSV file in supplementary material. Corresponding author: Prof Andrew J Pollard, andrew.pollard@paediatrics.ox.ac.uk
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 with study protcol, and prospective study registry were used in data extraction and risk of bias assessment. The target sample size specified in the registry (n = 1200) was achieved (n = 1240). Pre-planned immunogenicity analyses for age subgroups and variants of concern were reported. The primary outcome in the report (non-inferiority of anti-spike IgG antibodies) did not fully reflect that in the registry (humoral immune response).