Skip to main content
OpenTrials
Completed

NCT Number: NCT01331837

A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors

This randomized, open-label, parallel-group, multicenter study will evaluate the rate of cardiovascular events with tocilizumab in comparison to etanercept in participants with rheumatoid arthritis (RA). Participants will be randomized to receive intravenous (IV) 8 milligrams per kilogram (mg/kg) tocilizumab every 4 weeks or subcutaneous 50 milligrams (mg) etanercept weekly, with or without non-biologic disease-modifying anti-rheumatic drug (DMARD).

Completed

Looking for future studies?

Notify Me

Key information

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

APRILLUS, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with moderate to severe RA of greater than or equal to (>=6) months duration
  • Inadequate response to at least one non-biologic DMARD
  • Positive for Rheumatoid Factor (RF) and/or anti-cyclic citrullinated peptide (CCP) antibodies at screening
  • Have C-reactive protein (CRP) greater than (>) 0.3 milligrams per deciliter (mg/dL) at screening or at the baseline visit
  • Swollen joint count (SJC) >=8 (66 joint count) and tender joint count (TJC) >= 8 (68 joint count) during screening or at the baseline visit
  • History of Coronary Heart Disease (CHD) or presence of one or more additional CHD risk factors, including current cigarette smoking, hypertension, low High Density Lipoprotein (HDL) cholesterol, family history of premature CHD, diabetes, presence of extra-articular disease associated with rheumatoid arthritis
  • At the time of randomization, will have discontinued infliximab, adalimumab, golimumab, or certolizumab for >= 4 weeks

Exclusion criteria

  • Major surgery (including joint surgery or coronary revascularization) within 8 weeks prior to screening or planned major surgery within 1 year of study start
  • Rheumatic autoimmune disease other than RA
  • History of or current inflammatory joint disease other than RA
  • Current or recent (within past 3 months) evidence of serious uncontrolled concomitant cardiovascular or cerebrovascular disease (myocardial infarction, revascularization, stroke, transient ischemic attack, or acute coronary syndrome)
  • Current or previous (within the past 2 years) evidence of serious uncontrolled concomitant pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal disease
  • Uncontrolled disease states, such as asthma or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
  • Pre-existing central nervous system demyelinating or seizure disorders
  • History of diverticulitis, diverticulosis requiring treatment or other lower gastrointestinal tract conditions that might predispose to perforations
  • Current liver disease as determined by the investigator; a history of asymptomatic elevations in liver function tests (LFTs) is not considered an exclusion
  • Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds
  • Any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening or oral antibiotics within two weeks prior to screening visit
  • Active tuberculosis (TB) requiring treatment within 3 years prior to baseline
  • Latent TB diagnosed during screening that has not been appropriately treated
  • Primary or secondary immunodeficiency (history of or currently active)
  • Moderate to severe heart failure
  • Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years
  • Breast feeding mothers
  • History of alcohol, drug or chemical abuse within the 6 months prior to screening
  • Participants with lack of peripheral venous access
  • Participants with a history of allergic reactions to latex
  • Previous treatment with non-tumor necrosis factor (non-TNF)-inhibitor biologic therapy
  • Treatment with any investigational agent within 4 weeks of screening visit
  • Treatment with any cell depleting therapies within 1 year of baseline
  • Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline visit
  • Immunization with a live/attenuated vaccine within 4 weeks prior to baseline visit
  • Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation

Treatment and study plan

etanercept

Drug

Participants will receive 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.

Tocilizumab

Drug

Participants will receive 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.

Other names: Actemra

Primary outcomes

  1. Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke.

  2. Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event

    Time frame: From baseline up to 4.9 years

    Percentage of patients reporting any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke

  3. Time to First CV-EAC Adjudicated Event - Sensitivity Analysis

    Time frame: From Baseline up to 4.9 years

    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis

  4. Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis

    Time frame: From Baseline up to 4.9 years

    Percentage of patients with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analysis

  5. Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses

  6. Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis

    Time frame: From baseline up to 4.9 years

    Percentage of patients with any component of the composite of CV death (excluding events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke - Sensitivity Analyses

  7. Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date

    Time frame: From Baseline up to 4.9 years

    Prospective comparison of time to first occurrence of any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).

  8. Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date

    Time frame: From Baseline up to 4.9 years

    Percentage of participants with any component of the composite of CV death (including events adjudicated as 'Undetermined Cause of Death'), non-fatal myocardial infarction, or non-fatal stroke before last direct contact date (i.e., latest date of visit, IVRS call, or site call).

Secondary outcomes

  1. The Time to First Occurrence of an Expanded CV Composite Endpoint

    Time frame: From baseline up to 4.9 years

    Prospective comparison of the time to first ccurrence of the expanded composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.

  2. Percentages of Participants With an Expanded CV Composite Endpoint

    Time frame: From baseline up to 4.9 years

    Percentages of participants with the expanded CV composite endpoint. The expanded composite endpoint is defined as the CV composite of the primary endpoint with the addition of non-elective coronary revascularization procedures and hospitalization for unstable angina.

  3. Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal Myocardial Infarction

  4. Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction

    Time frame: From baseline up to 4.9 years

    Percentage of patients reporting Individual component of primary endpoint: non-fatal Myocardial Infarction

  5. Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of Individual component of primary endpoint: cardiovascular death

  6. Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death

    Time frame: From baseline up to 4.9 years

    Percentage of patients reporting Individual component of primary endpoint: cardiovascular death

  7. Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of Individual component of primary endpoint: non-fatal stroke

  8. Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke

    Time frame: From baseline up to 4.9 years

  9. Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality

    Time frame: From baseline up to 4.9 years

    Prospective comparison of time to first occurrence of Individual component of primary endpoint: All-cause mortality

  10. Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality

    Time frame: From baseline up to 4.9 years

    Percentage of patients reporting Individual component of primary endpoint: All-cause mortality

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Clinical Outcomes Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab (TCZ) in Comparison With Etanercept (ETA) on the Rate of Cardiovascular Events in Patients With Moderate to Severe Rheumatoid Arthritis (RA)

Important dates

Study start
2011
Primary completion
2016
Study completion
2016
First posted
Apr 8, 2011
Registry last updated
Jul 13, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.