<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02246257</url>
  </required_header>
  <id_info>
    <org_study_id>OdenseUH</org_study_id>
    <nct_id>NCT02246257</nct_id>
  </id_info>
  <brief_title>Early Rheumatoid Arthritis COR Intervention</brief_title>
  <acronym>ERACORI</acronym>
  <official_title>Multifactorial Intervention to Prevent Cardiovascular Disease in Patients With Early Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MD, PhD, Annemarie Lyng Svensson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of our present study is to evaluate the effect of a targeted, intensified,&#xD;
      multidimensional intervention compared to conventional treatment of modifiable risk factors&#xD;
      for CVD in patients with early RA. The primary endpoint, a composite of death from&#xD;
      cardiovascular causes, non-fatal MI, non-fatal stroke and re-vascularisation, will be&#xD;
      assessed after 5years' follow-up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a prospective randomised open, blinded endpoint trial with balanced&#xD;
      randomisation (1:1) conducted in seven outpatient clinics in Denmark. Follow-up visits for&#xD;
      patients in the intervention group are scheduled to occur at baseline and then after 2, 4 and&#xD;
      12 weeks and thereafter every third month for 5 years after randomisation. The control group&#xD;
      will be monitored for RA disease activity and comorbidity after 2, 4 weeks, 12 weeks and&#xD;
      thereafter following national guidelines for RA. Prevention of CVD risk factors in the&#xD;
      control group will be treated in general practice according to national guidelines for&#xD;
      diabetes (2011), hypertension (2009) and CVD (2013).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Major Cardiac Event (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularization)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Death Due to Any Cause</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Non-cardiovascular Death</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Serious Adverse Event (hospitalizations)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Time from randomization to the first venous thromboembolic event. Kaplan-Meier estimate of the mean</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients having a treatment success</measure>
    <time_frame>1, 2 and 5 years</time_frame>
    <description>LDL cholesterol &lt; 2.5 mmol/l&#xD;
HbA1c &lt; 48 mmol/mol (HbA1c &lt; 6.5%),&#xD;
Blood pressure &lt; 140/90 mmHg for non-diabetic patients and &lt; 130/80 mm Hg for diabetic patients and normoalbuminuria (urinary albumin creatinine ratio &lt; 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.&#xD;
Low RA disease activity DAS28-CRP &lt; 3.2 and DAS28-CRP &lt; 2.6 at 12, 24 and 60 months. Furthermore, all to hospitalisations will be adjudicated by the event committee</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>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.&#xD;
Hyperlipidaemia: LDL &gt; 2.5 is treated with 40 mg Simvastatin; Hypertension: BT &gt; 140/90 mmHg treated with 100 mg OD Losartan; Diabetes: DM BT &gt; 130/80 mmHg treated with 100 mg OD Losartan; Microalbuminuria: Urinary albumin creatinin ratio &gt; 30 mg treated with 100 mg OD Losartan; Hyperglycaemia: HBA1C &gt; 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks Metformin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>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.&#xD;
Hyperlipidaemia: LDL &gt; 2.5 is treated with 40 mg Simvastatin; Hypertension: BT &gt; 140/90 mmHg treated with 100 mg OD Losartan; Diabetes: DM BT &gt; 130/80 mmHg treated with 100 mg OD Losartan; Microalbuminuria: Urinary albumin creatinin ratio &gt; 30 mg treated with 100 mg OD Losartan; Hyperglycaemia: HBA1C &gt; 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks Metformin</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>LDL &gt; 2.5 is treated with 40 mg</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Hyperlipidaemia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <description>BT &gt; 140/90 mmHg treated with 50 mg OD</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Hypertension</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <description>DM BT &gt; 130/80 mmHg treated with 50 mg OD</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Diabetes</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <description>Microalbuminuria (urinary albumin creatinin ratio &gt; 30 mg) treated with 100 mg OD</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Microalbuminuria</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>HBA1C &gt; 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Hyperglycaemia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Outpatient rheumatology department</intervention_name>
    <description>(4 times yearly)</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Intervention</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Refered to general practice</intervention_name>
    <arm_group_label>Control</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  RA according to the revised American College of Rheumatology (ACR) 2010 criteria and&#xD;
             plasma LDL &gt; 2.5mmol/l.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Lactation&#xD;
&#xD;
          -  Ongoing/previous DMARD therapy&#xD;
&#xD;
          -  Ongoing/previous steorid therapy&#xD;
&#xD;
          -  Contraindication to any of the trial drugs&#xD;
&#xD;
          -  Current infection with parvovirus B19, hepatitis B, hepatitis C or human immune&#xD;
             deficiency virus. Previous report of hospitalisation for myocardial ischaemia defined&#xD;
             as follows: a) non-fatal myocardial infarction (MI) defined according to national and&#xD;
             international guidelines. b) Acute coronary syndrome (ACS) including acute ischaemic&#xD;
             symptoms with possible biomarker changes or elctrocardiographic changes that to not&#xD;
             meet the criteria for MI, c) angina pectoris, d) revascularisation (percutaneous&#xD;
             coronary intervention (PCI) or coronary artery bypass grafting (CABG).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Torkell J Ellingsen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Odense University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Annemarie L Svensson, MD, PhD</last_name>
    <phone>+45 28 555 126</phone>
    <email>lyng.annemarie@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Torkell J Ellingsen, MD, PhD</last_name>
    <phone>+45 6541 1814</phone>
    <email>torkell.ellingsen@rsyd.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Rheumathology, Frederiksberg and Bispebjerg univeristy Hospital</name>
      <address>
        <city>Frederiksberg</city>
        <state>Region Of Copenhagen</state>
        <zip>2000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Annemarie Lyng Svesson, MD, PhD</last_name>
      <phone>004528555126</phone>
      <email>lyng.annemarie@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Torkell J Ellingsen, MD, PhD, Professor</last_name>
      <phone>004565413523</phone>
      <email>torkell.ellingsen@rsyd.dk</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>May 20, 2022</last_update_submitted>
  <last_update_submitted_qc>May 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>MD, PhD, Annemarie Lyng Svensson</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Losartan</mesh_term>
    <mesh_term>Simvastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02246257
org study id: OdenseUH
nct id: NCT02246257
lead sponsor: 
has dmc: Yes
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Time to Major Cardiac Event (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularization)
time frame: Up to 5 years
description: 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.
measure: Time to Death Due to Any Cause
time frame: Up to 5 years
description: 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
measure: Time to Non-cardiovascular Death
time frame: Up to 5 years
description: 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
measure: Time to Serious Adverse Event (hospitalizations)
time frame: Up to 5 years
description: Time from randomization to the first venous thromboembolic event. Kaplan-Meier estimate of the mean
measure: The proportion of patients having a treatment success
time frame: 1, 2 and 5 years
description: 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
arm group label: Intervention
arm group type: Other
description: 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
arm group label: Control
arm group type: Other
description: 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
intervention type: Other
intervention name: Simvastatin
description: LDL > 2.5 is treated with 40 mg
arm group label: Control
arm group label: Intervention
other name: Hyperlipidaemia
intervention type: Other
intervention name: Losartan
description: BT > 140/90 mmHg treated with 50 mg OD
arm group label: Control
arm group label: Intervention
other name: Hypertension
intervention type: Other
intervention name: Losartan
description: DM BT > 130/80 mmHg treated with 50 mg OD
arm group label: Control
arm group label: Intervention
other name: Diabetes
intervention type: Other
intervention name: Losartan
description: Microalbuminuria (urinary albumin creatinin ratio > 30 mg) treated with 100 mg OD
arm group label: Control
arm group label: Intervention
other name: Microalbuminuria
intervention type: Other
intervention name: Metformin
description: HBA1C > 48 mmol/mol treated with 500 mg increased dose to 2,000 mg in 4 weeks
arm group label: Control
arm group label: Intervention
other name: Hyperglycaemia
intervention type: Other
intervention name: Outpatient rheumatology department
description: (4 times yearly)
arm group label: Intervention
other name: Intervention
intervention type: Other
intervention name: Refered to general practice
arm group label: Control
other name: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Torkell J Ellingsen, MD, PhD
role: Principal Investigator
affiliation: Odense University Hospital
last name: Annemarie L Svensson, MD, PhD
phone: +45 28 555 126
email: lyng.annemarie@gmail.com
last name: Torkell J Ellingsen, MD, PhD
phone: +45 6541 1814
email: torkell.ellingsen@rsyd.dk
facility: 
status: Recruiting
contact: 
contact backup: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Odense University Hospital
investigator full name: MD, PhD, Annemarie Lyng Svensson
investigator title: MD, PhD
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Cardiovascular Diseases
mesh term: Metformin
mesh term: Losartan
mesh term: Simvastatin
sharing ipd: Undecided