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

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.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Diseases; Hypertension; Diabetes; Dyslipidemias; Gout; Behavior, Smoking
• Intervention / Treatment: Other: URICORI; Other: CONTROL

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Management by Rheumatologist; Treatment of modifiable risk factors for cardiovascular disease managed by the Rheumatologist according to national guideline.	Other: URICORI; Treatment for cardiovascular risk factors according to national guideline administered at the department of Rheumatology
Active Comparator: Management by General Practitioner; Treatment of modifiable risk factors for cardiovascular disease managed by the General Practitioner according to national guideline.	Other: CONTROL; Treatment for cardiovascular risk factors according to national guideline administered at the General Practitioner

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responders (Dichotomised: responder/non-responder)	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.	1 year from inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL Cholesterol	Change from baseline of LDL Cholesterol (mmol/L)	1 year from inclusion
HbA1c	Change from baseline of HbA1c (mmol/mol).	1 year from inclusion
Systolic blood pressure	Change from baseline Systolic blood pressure (mmHg).	1 year from inclusion
Diastolic blood pressure Change from baseline Diastolic blood pressure (mmHg).	Change from baseline Diastolic blood pressure (mmHg)	1 year from inclusion
Smoking	Change in smoking status (dichotomised yes/no)	1 year from inclusion
Serum Urate	Change from baseline in serum urate (mmol/L)	1 year from inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL cholesterol	Proportion of participants achieving treatment target for LDL cholesterol (mmol/L)	1 and 5 years from inclusion
HbA1c	Proportion of participants achieving HbA1c (mmol/mol) treatment target.	1 and 5 years from inclusion
Systolic blood pressure	Proportion of participants achieving treatment target for systolic blood pressure (mmHg)	1 and 5 years from inclusion
Diastolic blood pressure	Proportion of participants achieving treatment target for diastolic blood pressure (mmHg)	1 and 5 years from inclusion
Smoking	Proportion of participants with change in smoking status (commencement and cessation)	1 and 5 years from inclusion
Serum urate	Proportion of participants achieving serum urate < 36.0 mmol/l or if tophaceous disease serum urate < 0.30 mmol/l	1 and 5 years from inclusion
Cardiovascular event	Proportion of participants with any serious cardiovascular event during the first year of the URICORI trial.	1 year form inclusion
Serious cardiovascular event	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)	5 years from inclusion
Death	Death from any cause (death will be classified as due to either cardiovascular or non-cardiovascular)	5 years from inclusion
Hospitalisation	Hospitalisation due to elective or acute cardiovascular reasons during the URICORI trial.	5 years from inclusion

Collaborators and Investigators

• Sponsor: Torkell Ellingsen
• Collaborators: Odense University Hospital; University of Southern Denmark; Frederiksberg University Hospital; Region of Southern Denmark; Oak Foundation; The Danish Rheumatism Association
• Investigators: Principal Investigator: Melanie Morillon, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: May 17, 2020
• First Submitted That Met QC Criteria: July 2, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Cardiovascular Diseases; Dyslipidemias
• Other Study ID Numbers: OL10224607

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: If other research groups could benefit from the IPD (individual patient data ), the data will be shared after individual evaluation by the trial sponsor.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No