Early Rheumatoid Arthritis COR Intervention (ERACORI)

Multifactorial Intervention to Prevent Cardiovascular Disease in Patients With Early Rheumatoid Arthritis

The primary aim of our present study is to evaluate the effect of a targeted, intensified, multidimensional intervention compared to conventional treatment of modifiable risk factors for CVD in patients with early RA. The primary endpoint, a composite of death from cardiovascular causes, non-fatal MI, non-fatal stroke and re-vascularisation, will be assessed after 5years' follow-up.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Rheumatoid Arthritis
• Intervention / Treatment: Other: Simvastatin; Other: Losartan; Other: Losartan; Other: Losartan; Other: Metformin; Other: Outpatient rheumatology department; Other: Refered to general practice

Detailed Description

The study is a prospective randomised open, blinded endpoint trial with balanced randomisation (1:1) conducted in seven outpatient clinics in Denmark. Follow-up visits for patients in the intervention group are scheduled to occur at baseline and then after 2, 4 and 12 weeks and thereafter every third month for 5 years after randomisation. The control group will be monitored for RA disease activity and comorbidity after 2, 4 weeks, 12 weeks and thereafter following national guidelines for RA. Prevention of CVD risk factors in the control group will be treated in general practice according to national guidelines for diabetes (2011), hypertension (2009) and CVD (2013).

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annemarie L Svensson, MD, PhD; Phone Number: +45 28 555 126; Email: lyng.annemarie@gmail.com
• Study Contact Backup: Name: Torkell J Ellingsen, MD, PhD; Phone Number: +45 6541 1814; Email: torkell.ellingsen@rsyd.dk

Study Locations

• Denmark
  • Region Of Copenhagen
    • Frederiksberg, Region Of Copenhagen, Denmark, 2000
      • Recruiting
      • Department of Rheumathology, Frederiksberg and Bispebjerg univeristy Hospital
      • Contact: Annemarie Lyng Svesson, MD, PhD; Phone Number: 004528555126; Email: lyng.annemarie@gmail.com
      • Contact: Torkell J Ellingsen, MD, PhD, Professor; Phone Number: 004565413523; Email: torkell.ellingsen@rsyd.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• RA according to the revised American College of Rheumatology (ACR) 2010 criteria and plasma LDL > 2.5mmol/l.

Exclusion Criteria:

• Pregnancy
• Lactation
• Ongoing/previous DMARD therapy
• Ongoing/previous steorid therapy
• Contraindication to any of the trial drugs
• Current infection with parvovirus B19, hepatitis B, hepatitis C or human immune deficiency virus. Previous report of hospitalisation for myocardial ischaemia defined as follows: a) non-fatal myocardial infarction (MI) defined according to national and international guidelines. b) Acute coronary syndrome (ACS) including acute ischaemic symptoms with possible biomarker changes or elctrocardiographic changes that to not meet the criteria for MI, c) angina pectoris, d) revascularisation (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intervention; In the intervention group all patients will receive statins according to national guidelines. Stepwise introduction of pharmacological therapy targeting 1) hyperlipidaemia, 2) hypertension, 3) hyperglycaemia and 4) microalbuminuria and behaviour modification will be controlled by the project team in an outpatient rheumatology department. Hyperlipidaemia: LDL > 2.5 is treated with 40 mg Simvastatin; Hypertension: BT > 140/90 mmHg treated with 100 mg OD Losartan; Diabetes: DM BT > 130/80 mmHg treated with 100 mg OD Losartan; Microalbuminuria: Urinary albumin creatinin ratio > 30 mg treated with 100 mg OD Losartan; Hyperglycaemia: HBA1C > 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks Metformin	Other: Simvastatin; LDL > 2.5 is treated with 40 mg; Other Names: Hyperlipidaemia; Other: Losartan; BT > 140/90 mmHg treated with 50 mg OD; Other Names: Hypertension; Other: Losartan; DM BT > 130/80 mmHg treated with 50 mg OD; Other Names: Diabetes; Other: Losartan; Microalbuminuria (urinary albumin creatinin ratio > 30 mg) treated with 100 mg OD; Other Names: Microalbuminuria; Other: Metformin; HBA1C > 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks; Other Names: Hyperglycaemia; Other: Outpatient rheumatology department; (4 times yearly); Other Names: Intervention
Other: Control; In the control group patients will be refered to general practice for pharmacological therapy according to national guidelines targeting 1) hyperlipidaemia, 2) hypertension, 3) hyperglycaemia and 4) microalbuminuria. Hyperlipidaemia: LDL > 2.5 is treated with 40 mg Simvastatin; Hypertension: BT > 140/90 mmHg treated with 100 mg OD Losartan; Diabetes: DM BT > 130/80 mmHg treated with 100 mg OD Losartan; Microalbuminuria: Urinary albumin creatinin ratio > 30 mg treated with 100 mg OD Losartan; Hyperglycaemia: HBA1C > 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks Metformin	Other: Simvastatin; LDL > 2.5 is treated with 40 mg; Other Names: Hyperlipidaemia; Other: Losartan; BT > 140/90 mmHg treated with 50 mg OD; Other Names: Hypertension; Other: Losartan; DM BT > 130/80 mmHg treated with 50 mg OD; Other Names: Diabetes; Other: Losartan; Microalbuminuria (urinary albumin creatinin ratio > 30 mg) treated with 100 mg OD; Other Names: Microalbuminuria; Other: Metformin; HBA1C > 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks; Other Names: Hyperglycaemia; Other: Refered to general practice; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Major Cardiac Event (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularization)	Days from randomization to the first of cardiac event. If no event, censoring occurs at earliest of termination date or efficacy cut-off date of 31 December 2020. Events will be adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Death Due to Any Cause	Days from randomization to death. If no death then censoring occurs at earliest of termination date or efficacy cutoff date of 31 Dec 2020. Kaplan-Meier estimate of the mean	Up to 5 years
Time to Non-cardiovascular Death	Days from randomization to death from a non-cardiovascular cause. If no event, then censoring occurs at earliest of termination date or efficacy cutoff date of 31 Dec 2020. Events will be adjudicated by an endpoint committee. Kaplan-Meier estimate of the mean	Up to 5 years
Time to Serious Adverse Event (hospitalizations)	Time from randomization to the first venous thromboembolic event. Kaplan-Meier estimate of the mean	Up to 5 years
The proportion of patients having a treatment success	LDL cholesterol < 2.5 mmol/l; HbA1c < 48 mmol/mol (HbA1c < 6.5%),; Blood pressure < 140/90 mmHg for non-diabetic patients and < 130/80 mm Hg for diabetic patients and normoalbuminuria (urinary albumin creatinine ratio < 30 mg/g) after 1-year of follow-up this in agreement with present national guidelines, which will be adjusted accordingly to any future changes in the respective national guidelines.; Low RA disease activity DAS28-CRP < 3.2 and DAS28-CRP < 2.6 at 12, 24 and 60 months. Furthermore, all to hospitalisations will be adjudicated by the event committee	1, 2 and 5 years

Collaborators and Investigators

• Sponsor: MD, PhD, Annemarie Lyng Svensson
• Investigators: Principal Investigator: Torkell J Ellingsen, MD, PhD, Odense University Hospital

Publications and helpful links

General Publications

• Svensson AL, Christensen R, Persson F, Logstrup BB, Giraldi A, Graugaard C, Fredberg U, Blegvad J, Thygesen T, Hansen IM, Colic A, Bagdat D, Ahlquist P, Jensen HS, Horslev-Petersen K, Sheetal E, Christensen TG, Svendsen L, Emmertsen H, Ellingsen T. Multifactorial intervention to prevent cardiovascular disease in patients with early rheumatoid arthritis: protocol for a multicentre randomised controlled trial. BMJ Open. 2016 Apr 20;6(4):e009134. doi: 10.1136/bmjopen-2015-009134.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: September 17, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimate): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Cardiovascular Diseases; Arthritis; Arthritis, Rheumatoid; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Metformin; Losartan; Simvastatin
• Other Study ID Numbers: OdenseUH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED