The DaRe2 approach (healthcare Data for pragmatic clinical Research in the NHS - primary 2 secondary) is designed to operationalise efficient, nationwide, primary care approaches for randomised trials embedded within the UK National Health Service (NHS), providing automated screening, targeted patient enrolment and 'no-visit' follow-up through innovations in big data and technology solutions.
DaRe2THINK will be the first exemplar of this system, and is appropriately focused on the intersection of key national priorities for healthcare; atrial fibrillation (a heart rhythm condition that will double in prevalence in the next few decades) and the impact this condition has on stroke, thromboembolic events, cognitive impairment and vascular dementia. The trial will test the hypothesis that direct oral anticoagulants (DOACs), now commonly used in older patients with atrial fibrillation (AF), are effective and cost-effective at reducing major adverse clinical events in younger patients at low or intermediate risk of stroke, and can reduce the high rate of cognitive decline. The health technology innovations noted above will allow the investigators to answer this important clinical question, as well as demonstrate the capacity and potential of this system for future, large-scale healthcare-embedded clinical trials for patient benefit.
Diagnosis of AF (previous, current or chronic)
Age at enrolment ≥55 years to ≤73 years
Prior documented stroke, transient ischaemic attack or systemic thromboembolism.
Combination of multiple known risk factors for stroke where oral anticoagulation would ordinarily be started, including: Heart failure; Hypertension; Age 65 years or older; Diabetes mellitus; Previous myocardial infarction, peripheral artery disease or aortic plaque; and/or Female gender.
Any prior history of intracranial bleeding.
Prior major bleeding requiring hospitalisation in the last 3 years.
Parallel
Direct Oral Anticoagulants
Drugchoice of DOAC (apixaban, dabigatran, edoxaban or rivaroxaban) according to local practice
Composite primary endpoint - Time to first event
Composite primary endpoint - Time to first event of cardiovascular mortality, ischaemic cerebrovascular events (stroke and transient ischaemic attacks), all thromboembolic events (including venous and arterial thromboembolism), myocardial infarction and vascular dementia
Change in cognitive function using the UK Biobank fluid intelligence/reasoning test (mixed-effects repeated measures analysis)
Change in cognitive function using the UK Biobank fluid intelligence/reasoning test (mixed-effects repeated measures analysis)
Change in cognitive function using the UK Biobank trail making test (mixed-effects repeated measures analysis)
Change in cognitive function using the UK Biobank trail making test (mixed-effects repeated measures analysis)
Change in cognitive function using the UK Biobank symbol digit substitution test (mixed-effects repeated measures analysis)
Change in cognitive function using the UK Biobank symbol digit substitution test (mixed-effects repeated measures analysis)
. Change in cognitive function using the UK Biobank non-verbal fluid reasoning matrices test (mixed-effects repeated measures analysis)
. Change in cognitive function using the UK Biobank non-verbal fluid reasoning matrices test (mixed-effects repeated measures analysis)
Potential participants located by CPRD
Number/proportion of potential participants located by CPRD and notified to the lead NIHR Clinical Research Network (CRN)
Primary care practices completing sign up
Number/proportion of primary care practices that have completed sign-up processes
Patients on automated screening successfully recruited
Number/proportion of patients eligible on automated screening that are successfully recruited
Rate of patient recruitment
Rate of patient recruitment
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University of Birmingham
Lead sponsor
Clinical Practice Research Datalink
Collaborator
University Hospital Birmingham NHS Foundation Trust
Collaborator
University of Oxford
Collaborator
London School of Economics and Political Science
Collaborator
Aston University
Collaborator
