Status: Ongoing
First registered on:
07/10/2021
Last updated on:
12/05/2023
1. Study identification
EU PAS Register NumberEUPAS43556
Official titleA post-authorisation/post-marketing observational study to evaluate the association between exposure to AZD1222 and safety concerns using existing secondary health data sources (COVID-19)
Study title acronym
Study typeObservational study
Brief description of the studyAstraZeneca developed vaccine AZD1222 to prevent COVID-19 (called Vaxzevria® in Europe). Based on the EU RMP, safety concerns for AZD122 include nervous system disorders (including immune-mediated neurological conditions), vaccine-associated enhanced disease (including vaccine-associated enhanced respiratory disease), thrombocytopenia with associated bleeding, anaphylaxis, thrombosis, and ‘thrombosis with thrombocytopenia syndrome’(TTS). This PASS will evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following immunisation in the real-world setting.
The primary study objectives are to (1) describe baseline characteristics of all individuals who receive at least one dose of AZD1222 over the study period; (2) describe, among subjects who receive a first dose of AZD1222, the timing and type of second dose of any COVID-19 vaccine over the study period; (3) describe the incidence of prespecified AESIs in subjects who have received at least one dose of AZD1222 and in matched unvaccinated subjects; and (4) estimate any increased risk of prespecified AESIs following vaccination with AZD1222 using study retrospective cohort and self-controlled risk interval designs. Secondary objectives are identical to the primary, although focused on specific populations considered to have missing information, specifically (a) women who are pregnant or breastfeeding, (b) immunocompromised patients, (b) frail patients with certain comorbidities, (c) patients with autoimmune or inflammatory disorders, and (d) patients who, at cohort entry, had recently received a number of selected vaccines to prevent diseases other than COVID-19.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)?
EU RMP category 3 (required)
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicableClinicalTrials.gov Identifier: NCT05126992;
https://clinicaltrials.gov/ct2/show/NCT05126992?term=NCT05126992&draw=2&rank=1
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsRTI-HS
Department/Research groupPharmacoepidemiology & Risk Management
Organisation/affiliationRTI Health Solutions
Details of (Primary) lead investigator
Title Dr
Last name Rebordosa
First name Cristina
Is this study being carried out with the collaboration of a research network?
Yes
Other centres where this study is being conducted
Multiple centres
In total how many centres are involved in this Study?7
Foundation for the Promotion of Health and Biomedical Research of the Valencia Region (FISABIO), Spain
Countries in which this study is being conducted
International study
Italy
Netherlands
Spain
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed09/08/202107/09/2021
Start date of data collection17/02/202218/02/2022
Start date of data analysis
Date of interim report, if expected22/04/202226/04/2022
Date of final study report25/06/2024
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companiesAstraZeneca AB100
Charities
Government body
Research councils
EU funding scheme
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Rebordosa
First name Cristina
Address line 1Av. Diagonal, 605, 9-1
Address line 2
Address line 3
CityBarcelona
Postcode08028
CountrySpain
Phone number (incl. country code)34933622807
Alternative phone number
Fax number (incl. country code)34937608507
Public Enquiries
Title Dr
Last name Rebordosa
First name Cristina
Address line 1Av. Diagonal, 605, 9-1
Address line 2
Address line 3
CityBarcelona
Postcode08028
CountrySpain
Phone number (incl. country code)34933622807
Alternative phone number
Fax number (incl. country code)34937608507
6. Study drug(s) information
Substance class (ATC Code)J07BX03 (covid-19 vaccines)
7. Medical conditions to be studied
Medical condition(s)Yes
COVID-19 immunisation
8. Population under study
Age
Adults (18 - 44 years)
Adults (45 - 64 years)
Adults (65 - 74 years)
Adults (75 years and over)
Sex
Male
Female
Other population
Immunocompromised
Pregnant women
9. Number of subjects
Estimated total number of subjects5200000
Additional information
Estimate based on exposure data as of April-June 2021; exact number will depend on number of individuals vaccinated during the study period. The source population for the study includes approximately 33.8 million subjects. All available data in each set will be used to identify subjects who received any SARS-CoV-2 vaccine.
10. Source of data
Is this study being carried out with an established data source?Yes
Data sources registered with ENCePP
Data sources not registered with ENCePP
Valencia Health System Integrated (VID) databases, Spain
Sources of data
Disease/case registry
Administrative database, e.g. claims database
Routine primary care electronic patient registry
Pharmacy dispensing records
11. Scope of the study
What is the scope of the study?
Disease epidemiology
Risk assessment
Drug utilisation study
Primary scope : Risk assessment
12. Main objective(s)
What is the main objective of the study?
To evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following the administration of at least one dose of the AZ COVID-19 vaccine in the real-world setting.
Are there primary outcomes?Yes
Adverse events of special interest (AESIs) and other safety concerns listed in Table 2 of the study protocol.
Are there secondary outcomes?No
13. Study design
What is the design of the study?
Cohort study
Self controlled case-series
Drug utilisation study
14. Follow-up of patients
Will patients be followed up?Yes
Please describe duration of follow up
Follow-up time will start on the date that all inclusion criteria are met and will end at the earliest of the occurrence of censoring conditions or the last data extraction/data availability as defined in the protocol for each study design.
15. Data analysis plan
Please provide a brief summary of the analysis method
Baseline characteristics will be described overall and in sequential periods overtime. For the cohort study, exposure propensity scores will be used to exclude noncomparable subjects and refine the balance between study cohorts, initially matched on calendar date of vaccination, age, and gender. Propensity scores will be used to control for confounding either by matching or by analytic methods involving stratification or weighting. For AESIs for which the risk interval is characterised, crude IRs and 95%CIs for the vaccinated population and for the comparator cohort will be estimated. Poisson regression models will be used to estimate crude and adjusted IRRs and IR differences with 95%CIs comparing vaccinated and comparator cohorts. Cox regression models will be used to estimate crude and adjusted hazard ratios and 95% CIs. For comparative analysis using the SCRI approach, conditional Poisson regression will be used to estimate IRRs and 95%CIs of specific AESIs, where appropriate.
16. ENCePP seal
Are you requesting the ENCePP seal for this study?
No
17. Full protocol
18. Study Results
Not submitted
Please list the 5 most relevant publications using data from your study
ReferenceLink to web-publication
None
19. Other relevant documents
Conflict(s) of interest of
investigator(s)Not submitted
Composition of Steering Group and
ObserversNot submitted
Other documents
DescriptionDocumentLatest version
Signed Code of
Conduct Checklist
Not submitted
Signed Code of Conduct Declaration
Not submitted
Signed Checklist for Study
Protocols
Not submitted
