DaRe2THINK is a MHRA (CTA 21761/0364/001-0001), and REC (21/NE/0021) approved randomised control trial. This application is seeking approval to link CPRD primary care data with both HES Admitted Patient Care and ONS Death Registration data to revolutionise the way that research is conducted in the NHS. Current RCT methodology often leads to recruitment of highly selected participants with less diversity than the clinical population. New RCT approaches are needed that can realise the value of the world-leading data quality and infrastructure of the NHS.
Atrial Fibrillation (AF) is the most common heart rhythm abnormality, is expected to double in prevalence in the next few decades, and leads to a considerable burden for patients and society at-large. In particular, the impact of stroke, and vascular dementia are all major public health concerns.
DaRe2THINK will test the hypothesis that direct oral anticoagulant (DOACs) are effective and cost-effective in patients with AF at low or intermediate risk of stroke by using an ambitious and innovative data-enabled approach through the Clinical Practice Research Datalink (CPRD) in General Practices across England.
This Individual-patient, open-label, event-driven RCT with 1:1 allocation to DOAC or usual care will run for a total of 60 months. Patient recruitment will last for 24 months and will be conducted through automated screening of over 10million health records found in the CPRD Primary Care database. Participants will be consented, randomised and followed up for 36 months through the linkage of their Primary and Secondary Care data. The primary outcome is a comprehensive composite of any thromboembolic event, including cardiovascular mortality, ischaemic stroke, pulmonary or venous thromboembolism, myocardial infarction and vascular dementia, ascertained entirely using electronic healthcare records within both Primary and Secondary NHS care. We will also assess and validate safety outcomes relating to any change in bleeding risk.
The primary outcome is a composite of cardiovascular mortality, ischaemic cerebrovascular events (stroke and transient ischaemic attacks), all thromboembolic events (including venous and arterial thromboembolism), myocardial infarction and vascular dementia.
Individual components of the primary outcome; Cumulative event rates for each individual component of the primary outcome; Conventional major adverse cardiovascular events (composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death); Any major bleeding or clinically-relevant non-major bleeding that requires hospitalisation; Minor bleeding that requires attention from primary care (any bleeding that leads to a primary care consultation); Haemorrhagic stroke and other types of intracranial bleeding; All-cause general practice visits; All-cause hospital admissions and duration of stay; Heart failure hospitalisation and duration of stay; All-cause mortality.
Dipak Kotecha - Chief Investigator - University of Birmingham
Alastair Mobley - Corresponding Applicant - University of Birmingham
David Shukla - Collaborator - University of Birmingham
Puja Myles - Collaborator - CPRD
Samir Mehta - Collaborator - University of Birmingham
Susan Beatty - Collaborator - CPRD
Tim Williams - Collaborator - CPRD
Xiaoxia Wang - Collaborator - University Hospitals Birmingham