Covid-19 Living Data

Trial ISRCTN89951424
Publication Clemens S, Nat. Commun., 2021
Dates: 2020-06-23 to 2020-12-01
Funding: Mixed (UKRI, NIHR, Wellcome Trust, CEPI, Lemann Foundation, Rede D’Or, and Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, and AstraZeneca)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Brazil Follow-up duration (months): 8.27
	ChAdOx1 (n=5207) Placebo (n=5209)
Inclusion criteria	Individuals aged 18 and over; Health professionals and/or adults at high risk of exposure to SARS-CoV-2; Able and willing (in the Investigator’s opinion) to comply with all study requirements; Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner/personal doctor and access all medical records when relevant to study procedures; For females of childbearing potential only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening and vaccination; Agreement to refrain from blood donation during the course of the study; Provide written informed consent
Exclusion criteria	Participation in COVID-19 prophylactic drug trials for the duration of the study (Participation in COVID-19 treatment trials is allowed in the event of hospitalisation due to COVID-19. The study team should be informed as soon as possible); Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study; Planned receipt of any vaccine (licensed or investigational), other than the study intervention, within 30 days before and after study vaccination; Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines); Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate; Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent severe infections and chronic use (more than 14 days) of immunosuppressant medication within the past 6 months except topical steroids or short-term oral steroids (course lasting ≤14 days); History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY or paracetamol; Any history of angioedema; Any history of anaphylaxis; Pregnancy, lactation or willingness/intention to become pregnant during the study; Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ); History of serious psychiatric condition likely to affect participation in the study; Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture; Suspected or known current alcohol or drug dependency; Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well-controlled comorbidities are allowed); History of laboratory-confirmed COVID-19; Seropositive for SARS-CoV-2 antibodies before enrolment; New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020, unless seronegative for SARS-CoV-2 antibodies at screening; Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban); Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
Interventions
	Intervention 2 IM doses of 3.5-6.5 x 10^10 vp, 4 to 12 weeks apart
	Control 1 IM dose of Men ACWY control vaccine and 1 IM dose of normal saline placebo, 4 to 12 weeks apart
Participants
	Randomized 10,416 participants
	Characteristics of participants Type of participants: Adults N=10,416 4268 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: 18+
	Description of participants Adults that were SARS-CoV-2 seronegative and with no history of COVID-19 in six centers in Brazil.
Primary outcome
	In the register Virologically confirmed (PCV positive) symptomatic cases of COVID-19 over the course of 12 months
	In the report Virologically-confirmed, symptomatic COVID-19, defined as a NAAT-positive swab combined with at least one of: fever >37.8ºC, cough, shortness of breath, anosmia or ageusia
Variants description
	Variants Gamma
	Description Efficacy analyses reported for Gamma (P.1), Zeta (P.2), B.1.1.28 lineage, B.1.1.33 lineage
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, when the trial is complete Data accessibility: Anonymised participant data will be made available when the trial is complete, upon requests directed to the corresponding author (Merryn Voysey, merryn.voysey@paediatrics.ox.ac.uk). Proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. After approval of a proposal, data can be shared through a secure online platform after signing a data access agreement. All data will be made available for a minimum of 5 years from the end of the trial.
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	Variant gamma: Some concerns
General comment	In addition to all available versions of the published/pre-print articles, the supplementary materials, study registry, protocol, and companion published article (Voysey, Lancet, 2020) were used in data extraction and risk of bias assessment. Following emergency use authorisation of ChAdOx1 nCoV-19 and an inactivated SARS-CoV-2 viral vaccine in Brazil on 17th January 2021, all trial participants were unblinded to vaccine allocation. Participants in the control group were offered 2 doses of ChAdOx1 nCoV-19 within the trial with a dose interval in line with the national programme or could choose to accept the inactivated viral vaccine as part of the Brazilian national immunisation programme. Post-hoc exploratory analysis with data cut-off date on February 28, 2021 at which point the majority of participants in the trial were unblinded and further accrual of cases for efficacy analyses were no longer possible.