Urica Cor Intervention (URICORI) Trial (URICORI)

A Multifactorial 'Urica Cor Intervention' to Prevent Cardiovascular Disease in People With Gout: Protocol for the Multicentre, Randomised Controlled, Blinded Endpoint URICORI Trial

Odense University Hospital, Frederiksberg University Hospital, Oak Foundation, The Danish Rheumatism Association, Region of Southern Denmark, University of Southern Denmark

The objective of the Urica Cor Intervention (URICORI) trial is to evaluate the effectiveness of a one-year, intervention of modifiable risk factors for CVD administered in a rheumatology outpatient clinical setting, compared with conventional treatment for modifiable risk factors for CVD in people with gout.

Introduction: Gout has been associated with a number of comorbidities including cardiovascular disease (CVD). Mounting evidence suggests that hyperuricaemia and gout are associated with a high risk for CVD. Gout is closely related to hypertension, dyslipidaemia, obesity and metabolic syndrome, all well-known factors contributing to the development of CVD. Gout management guidelines all agree that comorbidity screening is relevant and thus should be implemented in contemporary gout management. However, no specific strategy for management of CVD risk factors, in a gout population, exists. Objective: The objective of the Urica Cor Intervention (URICORI) trial is to evaluate the effectiveness of a one-year, intervention of modifiable risk factors for CVD administered in a rheumatology outpatient clinical setting, compared with conventional treatment for modifiable risk factors for CVD in people with gout. Design: The study is a randomised, open label, blinded endpoint trial, with balanced randomisation (1:1) conducted in four rheumatology outpatient clinics in Denmark. The investigators aim to recruit 266 people with gout, fulfilling the current EULAR ( European League against Rheumatism)/ ACR (American College of Rheumatology) gout classification criteria. Eligible patients will be randomised to receive either conventional (control group) treatment for CVD risk factors administered by their general practitioner according to national guidelines (NG) versus the URICORI programme, administered at the rheumatology department, targeting the same CVD risk factors according to NG. Both groups will be treated for gout at their local department of rheumatology. End Points: primary end point is a composite endpoint. By inclusion in the URICORI programme all participants will be considered a member of one of four categories derived from the Systematic Coronary Risk Estimation (SCORE) screening programme designed to assess the 10 year risk of fatal cardiovascular disease in European low risk population. As a consequence, participants will be classified as responder after 12 months if all national treatment targets for LDL cholesterol, HbA1c, Blood pressure (systolic and diastolic), according to their SCORE risk profile, is met and no commencement of smoking. If not, participants will be classified as non-responders. Key secondary end points: Change from baseline of LDL cholesterol, HbA1c, systolic blood pressure, diastolic blood pressure, smoking status and change from baseline in serum urate. Exploratory end points: Proportion of participants achieving treatment target for LDL cholesterol, HbA1c, systolic blood pressure, diastolic blood pressure, change in smoking status (commencement and cessation) and proportion of participants achieving serum urate < 36.0 mmol/l or serum urate < 0.30 mmol/l for tophaceous disease. After year 1 and year 5, the first occurrence of any serious cardiovascular event (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or urgent revascularization due to unstable angina) during the URICORI trial will be registered. Death and hospitalisation during the URICORI trial will also be evaluated after year 5. Events will be determined by medical record review and evaluated by the endpoint adjudication committee. The Outcome Measures in Rheumatology (OMERACT) endorsed Core Domain Set for us in trials in gout will measured during and after the one-year URICORI intervention trial. Ethics and dissemination: The local ethics committee in the region of southern Denmark and the Danish data agency in the region of southern Denmark will approve this protocol prior to commencement.

Treatment of modifiable risk factors for cardiovascular disease managed by the Rheumatologist according to national guideline.

Treatment of modifiable risk factors for cardiovascular disease managed by the General Practitioner according to national guideline.

Treatment for cardiovascular risk factors according to national guideline administered at the department of Rheumatology

Treatment for cardiovascular risk factors according to national guideline administered at the General Practitioner

Primary end point is a composite endpoint. By inclusion in the URICORI trial all participants will be considered a member of one of four categories derived from the Systematic Coronary Risk Estimation (SCORE - screening programme designed to assess the 10 year risk of fatal cardiovascular disease in European low risk population, range 0-24%). As a consequence, participants will be classified as responder after 12 months if all national treatment targets for LDL cholesterol, HbA1c, Blood pressure (systolic and diastolic), according to their SCORE risk profile, is met and no commencement of smoking. If not, participants will be classified as non-responders.

Proportion of participants achieving serum urate < 36.0 mmol/l or if tophaceous disease serum urate < 0.30 mmol/l

Proportion of participants with any serious cardiovascular event during the first year of the URICORI trial.

Proportion of patients with any serious cardiovascular event during the 5-year URICORI trial. (serious cardiovascular event: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or urgent revascularization due to unstable angina)

Death from any cause (death will be classified as due to either cardiovascular or non-cardiovascular)

Inclusion Criteria: Gout according to current EULAR/ACR (American College of Rheumatology) gout classification criteria Age >18 years Plasma LDL >3.0 mmol/L Agreeable to start treatment for CVD risk factors if indicated Ability to give informed consent Ability to communicate via telephone Exclusion Criteria: Other inflammatory diseases requiring immunosuppressant therapy. Age >70 years. Active cancer (in active treatment). Chronic kidney disease (eGFR <30 ml/min/1.73m2). People whose behaviour or lifestyle would render them less likely to comply with the study protocol (i.e., abuse of alcohol, substance misuse or debilitating psychiatric conditions). Familial hypercholesterolemia.

If other research groups could benefit from the IPD (individual patient data ), the data will be shared after individual evaluation by the trial sponsor.