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)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 3,080
- 试验地点
- 426
- 主要终点
- Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Etanercept
干预措施: Etanercept (Drug)
Tocilizumab
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Time to First CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
时间窗: 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
Percentage of Patients Reporting a Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
时间窗: 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
Time to First CV-EAC Adjudicated Event - Sensitivity Analysis
时间窗: 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
Time to First CV-EAC Adjudicated Event Before Last Direct Contact Date
时间窗: 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).
Percentage of Participants With a CV-EAC Adjudicated Event Before Last Direct Contact Date
时间窗: 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).
Time to First Cardiovascular (CV) Events Adjudication Committee (EAC) (CV-EAC) Adjudicated Event
时间窗: 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.
Percentage of Patients With a CV-EAC Adjudicated Event - Sensitivity Analysis
时间窗: 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
Percentage of Patients With a CV-EAC Adjudicated Event Excluding Undetermined Cause of Death - Sensitivity Analysis
时间窗: 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
次要结局
- The Time to First Occurrence of an Expanded CV Composite Endpoint(From baseline up to 4.9 years)
- Percentages of Participants With an Expanded CV Composite Endpoint(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Myocardial Infarction(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Cardiovascular Death(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Cardiovascular Death(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: Non-fatal Stroke(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: Non-fatal Stroke(From baseline up to 4.9 years)
- Time to First Occurrence of Individual Component of Primary Endpoint: All-cause Mortality(From baseline up to 4.9 years)
- Percentage of Patients With Individual Component of Primary Endpoint: All-cause Mortality(From baseline up to 4.9 years)