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Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events) (CANTOS)

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ClinicalTrials.gov Identifier: NCT01327846
Recruitment Status : Completed
First Posted : April 4, 2011
Results First Posted : January 22, 2020
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 29, 2011
First Posted Date  ICMJE April 4, 2011
Results First Submitted Date  ICMJE November 25, 2019
Results First Posted Date  ICMJE January 22, 2020
Last Update Posted Date January 22, 2020
Actual Study Start Date  ICMJE April 11, 2011
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components [ Time Frame: From randomization, to end of treatment plus 30 days, up to approximately 6 years ]
    Time to occurrence of CEC (Cardiovascular clinical events adjudication committee) confirmed MACE, which was a composite endpoint consisting of CEC confirmed CV death, CEC confirmed non-fatal MI,or CEC confirmed non-fatal stroke. Patients with the CEC adjudicated reason for death of "Unknown" were counted as CV (cardiovascular) death.
  • Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery [ Time Frame: 24 months ]
  • Substudy 2 (Core Phase): Change From Baseline of the Insulin Secretion Rate (ISR) Relative to Glucose 0-30 Min Defined as Φ30 = AUCISR 0-30 / AUCGluc 0-30 Averaged Across the Year 3, 4, 5 Visits [ Time Frame: From randomization up to approximately 6 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 31, 2011)		 Time to first occurrence of a major adverse cardiovascular event, which is a composite endpoint consisting of cardiovascular death, non-fatal MI, and stroke. [ Time Frame: 36 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
  • Patients With Core Phase CEC Confirmed CV Death, Non-fatal MI, Non-fatal Stroke, or Hospitalization for Unstable Angina Requiring Unplanned Revascularization [ Time Frame: From randomization, to end of treatment pus 30 days, up to approximately 6 years ]
    Occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina requiring unplanned revascularization. MACE includes CV death, non-fatal MI and non-fatal stroke. CEC = Clinical Endpoints Committee
  • Patients With Core Phase New Onset Type 2 Diabetes Among Patients With Pre-diabetes at Randomization [ Time Frame: From randomization up to approximately 6 years ]
    Time to CEC confirmed new onset of type 2 diabetes among those with pre-diabetes at randomization (i.e. excluding those that are normoglycemic at baseline)
  • Core Phase All-cause Mortality, Non-fatal MI, or Non-fatal Stroke [ Time Frame: From randomization, to end of treatment plus 30 days, up to approximately 6 years ]
    Occurrence of the composite endpoint consisting of all-cause mortality, non-fatal IM, or non-fatal stroke
  • Core Phase All-cause Mortality [ Time Frame: From randomization, to end of treatment plus 30 days, up to approximately 6 years ]
    Number of participant deaths
  • Summary of Adverse Events (Core Phase) [ Time Frame: From randomization, to end of treatment plus 30 days, up to approximately 6 years ]
    Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the double-blind Core phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
  • Summary of Adverse Events (Extension Phase) [ Time Frame: From start of Extension phase, to end of treatment plus 30 days, up to approximately 2 years ]
    Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs) occurring during the Extension phase of the study. AEs/SAEs are any signs or symptoms that occur during the study treatment.
  • Substudy 1 (Core Phase): Change From Baseline of the Total Vessel Wall Area at Month 3 in the Bifurcation Region of the Index Carotid Artery [ Time Frame: 3 months ]
  • Substudy 1 (Core Phase): Mean Total Vessel Wall Area Across the Left and Right Carotid Artery at Month 3 and Month 24 [ Time Frame: 24 months ]
  • Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries [ Time Frame: 24 months ]
  • Substudy 1 (Core Phase): The Existence of a Baseline Total Vessel Wall Area by Treatment Interaction as Well as the Consistency of the Treatment Effect Across Subgroups [ Time Frame: 24 months ]
  • Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index [ Time Frame: From randomization up to approximately 6 years ]
  • Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under Curve (AUC) 0-120 Min of Glucose Concentration, Insulin Concentration, Pro-insulin Concentration, and Insulin Concentration/Glucose Concentration Ratio [ Time Frame: From randomization up to approximately 6 years ]
  • Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio [ Time Frame: From randomization up to approximately 6 years ]
  • Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under the Curve (AUC) 0-120 Min of C-peptide Concentration [ Time Frame: From randomization up to approximately 6 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2011)
  • Time to the first occurrence of the composite cardiovascular endpoint consisting of cardiovascular death, non-fatal MI, stroke, and hospitalization for unstable angina requiring unplanned revascularization. [ Time Frame: 36 months ]
  • Time to new onset type 2 diabetes among those with pre-diabetes at randomization. [ Time Frame: 36 months ]
  • Time to first occurrence of non-fatal MI, stroke, and all-cause mortality composite. [ Time Frame: 36 months ]
  • Time to all-cause mortality. [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Event-driven Trial of Quarterly Subcutaneous Canakinumab in the Prevention of Recurrent Cardiovascular Events Among Stable Post-myocardial Infarction Patients With Elevated hsCRP
Brief 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.
Detailed Description Sub-study 1 and 2 were terminated prior to data collection from subjects. However, there is an ongoing extension trial where patients are receiving open-drug label.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Atherosclerosis
Intervention  ICMJE
  • Drug: Canakinumab
    Other Name: ACZ885
  • Drug: Placebo
  • Drug: Standard of care
    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
Study Arms  ICMJE
  • Experimental: Canakinumab Dose 50 mg

    Pivotal Phase:

    Blinded Canakinumab 50 mg quarterly subcutaneous + standard of care therapy.

    Extension Phase:

    Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

    Interventions:
    • Drug: Canakinumab
    • Drug: Standard of care
  • Experimental: Canakinumab Dose 150 mg

    Pivotal Phase:

    Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

    Interventions:
    • Drug: Canakinumab
    • Drug: Standard of care
  • Experimental: Canakinumab Dose 300 mg

    Pivotal Phase:

    Blinded Canakinumab 300 mg quarterly subcutaneous (with one additional dose at week 2) + standard of care therapy.

    Extension phase:

    Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

    Interventions:
    • Drug: Canakinumab
    • Drug: Standard of care
  • Placebo Comparator: Placebo

    Pivotal Phase:

    Blinded matching placebo quarterly subcutaneous + standard of care therapy.

    Extension Phase:

    Switched to open-label Canakinumab 150 mg quarterly subcutaneous + standard of care therapy

    Interventions:
    • Drug: Placebo
    • Drug: Standard of care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2020)		 10066
Original Estimated Enrollment  ICMJE
 (submitted: March 31, 2011)		 7302
Actual Study Completion Date  ICMJE April 14, 2019
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   China,   Colombia,   Croatia,   Czechia,   Estonia,   Germany,   Greece,   Guatemala,   Hungary,   Iceland,   India,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Netherlands,   Norway,   Peru,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Slovakia,   Slovenia,   South Africa,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Ecuador,   Former Serbia and Montenegro,   Israel
 
Administrative Information
NCT Number  ICMJE NCT01327846
Other Study ID Numbers  ICMJE CACZ885M2301
2010-022970-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP