Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)
Condition: Atherosclerosis
MeSH terms: Atherosclerosis
Intervention: Canakinumab; Placebo; Standard of care
Intervention description: Standard of care post-MI background therapy includes, but is not limited to, lipid lowering, anti-hypertensive, beta blockers, and anti-platelet therapy as appropriate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 10066.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cardiovascular Death; Myocardial Infarction; Stroke; Canakinumab; IL-1B; hsCRP

Summary:

      Main Study (CACZ885M2301): The purpose of the pivotal phase of this trial was to test the
      hypothesis that canakinumab treatment of patients with myocardial infarction (MI) at least
      one month prior to study entry and elevated hsCRP could prevent recurrent cardiovascular
      events.

      The purpose of the extension phase of the main study is to collect additional long-term
      safety data on continued exposure to canakinumab in patients who participated in the pivotal
      phase.

      Sub-study 1 (CACZ885M2301S1): The purpose of this sub-study was to evaluate the effect of
      quarterly subcutaneous canakinumab treatment for 24 months comparted with placebo on the
      carotid plaque burden measured by integrated vascular MRI in patients enrolled in the
      CACZ885M2301 study (CANTOS).

      Sub-study 2 (CACZ885M2301S2): The purpose of this CANTOS sub-study was to determine whether,
      in patients with type 2 diabetes participating in the CANTOS main study, canakinumab compared
      to placebo, on top of standard of care could increase insulin secretion and insulin
      sensitivity.
    

Eligibility criteria:

        Main Study Inclusion Criteria:

          -  Written informed consent

          -  Male, or Female of non-child-bearing potential

          -  Age ≥ 18 years.

          -  Spontaneous MI at least 30 days before randomization. hsCRP ≥ 2 mg/L

        Substudy 1 Inclusion:

          -  All Inclusion from Main Study

          -  Acquisition of evaluable baseline MRI images of bilateral carotid arteries by the
             imaging core laboratory

        Substudy 2 Inclusion:

          -  All inclusion from Main Study

          -  T2D at baseline per Main protocol criteria and be on a stable anti-hyperglycemic
             medication for at least 4 weeks prior to the baseline OGTT test

          -  Willing to have the OGTT assessment started before 10 am

        Main Study Exclusion Criteria:

          -  Pregnant or nursing (lactating) women

          -  Women of child-bearing potential

          -  Any of the following concomitant diseases

          -  Planned coronary revascularization (PCI or CABG)

          -  Major non-cardiac surgical or endoscopic procedure within past 6 months

          -  Multi-vessel CABG surgery within the past 3 years

          -  Symptomatic patients with Class IV heart failure (HF) (New York Heart Association
             [NYHA].

          -  Uncontrolled hypertension

          -  Uncontrolled diabetes

          -  History or evidence of active tuberculosis (TB) infection Substudy 1 Exclusion

          -  All Main exclusion

          -  Patients with prior history of carotid angioplasty, stenting, or carotid atherectomy

          -  Patients with contraindications to MRI examination (brain aneurysm clip, implanted
             neural stimulator, implanted cardiac pacemaker, pacemaker wires or defibrillator,
             prosthetic heart valves, cochlear implant, ocular foreign body or other implanted
             body, tattoos, implanted insulin pump, metal shrapnel or bullet)

          -  Patients prone to claustrophobia or known anxiety disorders

          -  BMI > 40 kg/m2 Substudy 2 Exclusion

          -  This sub-study does not have any additional exclusion criteria.