Covid-19 Living Data

Trial CTRI/2021/08/035648
Publication Rose W, Lancet Reg Health Southeast Asia, 2023
Dates: 2021-08-30 to 2022-01-19
Funding: Public/non profit (Azim Premji Foundation and Bill and Melinda Gates Foundation)
Conflict of interest: no COI

Methods
	RCT
	Location : Single center / India Follow-up duration (months): 3
	ChAdOx1/BBV152 boost (n = 99) ChAdOx1/ChAdOx1 boost (n = 101) BBV152/BBV152 boost (n = 103) BBV152/ChAdOx1 boost (n = 102)
Inclusion criteria	Adults above 18 years had received two primary homologous doses of COVISHIELDTM or COVAXIN® and had completed 12-36 weeks after their second dose No known immunodeficiency History of no contact with COVID-2019 persons within at least 14 days before the enrolment (according to subjects) No evident vaccine-induced reactions or complications after receiving immunobiological products in the medical history No acute infectious and/or respiratory diseases within at least 14 days before the enrolment.
Exclusion criteria	Previous receipt of any COVID vaccine (only for those who are in the prime and boost part of the study) Any vaccination/immunization within 30 days before the enrolment Steroids (except hormonal contraceptives) and/or immunoglobulins or other blood products therapy not finished 30 days before the enrolment Immunosuppressors therapy finished within 3 months before the enrolment Pregnancy or breast-feeding Acute coronary syndrome or stroke suffered less than one year before the enrolment Tuberculosis, chronic systemic infections Drug allergy – history of anaphylaxis, hypersensitivity or allergic reaction to immunobiological products, known allergic reactions to study product components, acute exacerbation of allergic diseases on the enrolment day Subjects who are on drugs that could have potential drug interactions with the vaccines: A.drugs for multiple sclerosis (dimethyl fumarate, fingolimod, ozanimod, etc.), B. monoclonal antibodies, corticosteroids, corticotropin, C. antineoplastic drugs, cytostatic agents (platinum-based drugs, bleomycin, taxanes, methotrexate, melphalan, capecitabine, carmustine, vincristine, vinblastine, cyclophosphamide, cyclosporine, docetaxel, doxorubicin, daunorubicin, fluorouracil, etc.) and target drugs (dasatinib, lenalidomide, nilotinib, pemetrexed, everolimus, sirolimus, asparaginase, bortezomib, etc.), D. immunoglobulins, interleukins, X-ray contrast agents Medical history of malignancy Donated blood or plasma (450+ mL) within 2 months before the enrolment Splenectomy in the medical history Neutropenia (absolute neutrophil count <1000 mm3, agranulocytosis, significant blood loss, severe anaemia (haemoglobin <80g/l) immunodeficiency including autoimmune disorders in the medical history within 6 months before the enrolment Known HIV positive Local inflammation at injection site (deltoid muscle area), which does not allow assessing the local response to the vaccine administration Alcohol or drug addiction in the medical history Participation in any other interventional clinical trial within 1 month prior to the screening Any other medical condition that would limit the participation of the subject as per Investigator’s discretion Subjects contraindicated for vaccination.
Interventions
	Intervention 1 IM booster dose of 0.5 mL BBV152, 12-36 weeks after ChAdOx1 primary schedule. 1 IM booster dose of 0.5 mL ChAdOx1, 12-36 weeks after BBV152 primary schedule.
	Control 1 IM booster dose of 0.5 mL ChAdOx1, 12-36 weeks after ChAdOx1 primary schedule.1 IM booster dose of 0.5 mL BBV152, 12-36 weeks after BBV152 primary schedule.
Participants
	Randomized 405 participants
	Characteristics of participants Type of participants: Adults N=405 240 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Adults that were SARS-CoV-2 infection-free in a single centre in India
Primary outcome
	In the register Immunogenicity measured by anti spike immunoglobulins for SARS CoV 2 Timepoint: boost Only - Day 28 after the booster dose ; Prime/boost - Day 28 after the second dose of the 2 primary vaccine doses
	In the report 1)Seropositivity on day 28 post booster.; 2)Incidence of related adverse events, serious adverse events following vaccination and any clinically significant change in the physical examination parameters and laboratory values.
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: No Data accessibility: Dr Winsley Rose, MD: winsleyrose@cmcvellore.ac.in
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	Low
General comment	In addition to the preprint article, the trial registry was used in data extraction and assessment of risk of bias. Neither protocol nor statistical analysis plan was available. Supplementary materials referred to in the article were not available via the pre-print host website at time of extraction. The trial was planned as open label in the registry but was reported as double-blind. The methods of randomization and masking in the report differ from those in the registry. The co-primary immunogenicity and safety outcomes in the article reflect include the immunogenicity primary outcome in the registry. It seems likely that the trial (n = 404) achieved its target sample size as the report included only four of twelve groups included in the registry, with a total target sample size of 1100. This trial was updated on April 24th 2023, after publication of the study report.