Association of the Risk for Thrombotic Thrombocytopenia Syndrome and Exposure To COVID-19 Vaccines

Study Overview
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Brief Summary
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Background/Rationale: A very rare syndrome of thrombosis associated with low platelets has been reported in a few cases of recent exposure to COVID-19 vaccine. This thrombotic thrombocytopenia syndrome seems to be affecting patients of all ages and both genders; at present there is no clear signal of risk factors. Objectives: To evaluate an association between COVID-19 vaccine exposure and thromboembolic events occurring with thrombocytopenia (thrombotic thrombocytopenia syndrome; TTS). Study design: Two primary study designs will be considered, a case control study and a self-controlled case series (SCCS). A cohort analysis will be considered, in addition or as an alternative to either of the primary study designs, pending feasibility assessment of the follow-up time. Data Source(s): Data for the study will be accessed through the NHS Digital Trusted Research Environment (TRE), providing national data coverage. Primary care data will be linked with vaccination, hospitalization, COVID-19 test results, mortality data. Initial exploratory analyses will be conducted using the Oxford-Royal College of General Practitioners sentinel network; ORCHID network database (N>15million). Subjects of interest are patients who have received a COVID-19 vaccine. However, investigators will require access to data from all subjects in the databases. Statistical Analysis: The study period will start on December 02, 2020, when the COVID-19 vaccine was first approved in the UK and will end at the end of data availability. For the case-control design, all cases of TTS will be matched with control using risk-set matching. A case or matched control will be considered exposed if a COVID-19 vaccination will be within risk interval prior to the diagnosis date of the matched case. For the SCCS, estimates of relative incidence (RI), in all risk intervals will be reported. For the retrospective cohort design, the incidence of TTS after receiving COVID-19 vaccine will be estimated and investigators will compare this incidence with that occurring in an unvaccinated comparator group about levels of infection across the whole population. Variables: Demographic, socioeconomic descriptors, clinical diagnosis, vaccines, potential confounders, thrombotic phenomena, COVID-19 infection, and other characteristics as applicable.

Official Title
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An Assessment of a Relationship Between the Exposure to COVID-19 Vaccines and Risk of Thrombotic Thrombocytopenia Syndrome ATTEST Study (Association of the Risk for Thrombotic Thrombocytopenia Syndrome and Exposure To COVID-19 Vaccines)

Conditions
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Covid-19

Intervention / Treatment
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* Other: Pre-COVID-19
* Other: COVID-19
* Other: COVID-19 vaccination roll-out


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A minimum of 12 months medical history prior to the start of the study period Exclusion Criteria: Less than 12 moths medical history prior to the start of the study period

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pre-COVID-19<br> | Other: Pre-COVID-19<br>* Pre-COVID-19 period<br>|
| COVID-19<br> | Other: COVID-19<br>* COVID-19 period<br>|
| COVID-19 vaccination roll-out<br> | Other: COVID-19 vaccination roll-out<br>* COVID-19 vaccination roll-out period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| thrombotic thrombocytopenia syndrome; TTS | This is to complete studies in NHS Digital and ORCHID data | 9 months |