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

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ClinicalTrials.gov Identifier: NCT01331837
Recruitment Status : Completed
First Posted : April 8, 2011
Results First Posted : July 13, 2017
Last Update Posted : July 13, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Etanercept Drug: Tocilizumab Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3080 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : August 2, 2011
Primary Completion Date : March 25, 2016
Study Completion Date : March 25, 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Etanercept Drug: Etanercept
Participants will receive 50 mg etanercept subcutaneously weekly until switch to another RA therapy or up to 4.9 years.
Experimental: Tocilizumab Drug: Tocilizumab
Participants will receive 8 mg/kg tocilizumab IV every 4 weeks until switch to another RA therapy or up to 4.9 years.
Other Name: Actemra


Outcome Measures

Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01331837


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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01331837     History of Changes
Other Study ID Numbers: WA25204
2010-020065-24 ( EudraCT Number )
First Posted: April 8, 2011    Key Record Dates
Results First Posted: July 13, 2017
Last Update Posted: July 13, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Etanercept
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors