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

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: April 7, 2011
Last updated: September 1, 2016
Last verified: September 2016
This randomized, open-label, parallel-group, multicenter study will evaluate the rate of cardiovascular events of tocilizumab in comparison to etanercept in participants with rheumatoid arthritis. Participants will be randomized to receive intravenous (IV) 8 milligrams per kilogram (mg/kg) tocilizumab every 4 weeks or subcutaneous 50 mg etanercept weekly, with or without non-biologic disease modifying anti-rheumatic drug (DMARD). The anticipated time on study drug is up to 5 years.

Condition Intervention Phase
Cardiovascular Disease, Rheumatoid Arthritis
Drug: Etanercept
Drug: Tocilizumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Time from randomization to occurrence of the primary major adverse cardiac events, defined as a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from randomization to occurrence of cardiovascular composite endpoint of major events, non-fatal coronary revascularization procedures and hospitalization for unstable angina [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 3140
Study Start Date: August 2011
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Etanercept Drug: Etanercept
50 mg subcutaneously weekly until switch to another RA therapy or up to 5 years.
Experimental: Tocilizumab Drug: Tocilizumab
8 mg/kg intravenously every 4 weeks until switch to another RA therapy or up to 5 years.
Other Name: RoActemra/Actemra


Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female participants, greater than or equal to (>/=) 50 years of age
  • Participants with moderate to severe rheumatoid arthritis of >/=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 a C-Reactive Protein (CRP) greater than (>) 0.3 milligrams per deciliter (mg/dL) at screening or at the baseline visit
  • Swollen joint count (SJC) and Tender joint count (TJC) >/= 8 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
  • Females of childbearing potential must have a negative pregnancy test within 28 days of randomization and must be ready to use reliable contraceptive methods

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 rheumatoid arthritis
  • History of, or current, inflammatory joint disease other than rheumatoid arthritis
  • 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 intravenous (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 six months prior to screening
  • Participants with lack of peripheral venous access
  • Participants with a history of allergic reactions to latex
  • Previous treatment with non-TNF-inhibitor biologic therapy
  • Treatment with any investigational agent within four 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 six months of baseline visit
  • Immunization with a live/attenuated vaccine within four weeks prior to baseline visit
  • Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01331837

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

Responsible Party: Hoffmann-La Roche Identifier: NCT01331837     History of Changes
Other Study ID Numbers: WA25204  2010-020065-24 
Study First Received: April 7, 2011
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Cardiovascular Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors processed this record on September 26, 2016