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Completed

NCT Number: NCT01327846

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

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.

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Key information

Conditions

Atherosclerosis Arterial Occlusive Diseases Arteriosclerosis Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Heart Diseases Infarction Ischemia Myocardial Infarction Myocardial Ischemia Necrosis Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Stroke Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Bahía Blanca, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Canakinumab

Drug

Other names: ACZ885

Placebo

Drug

Standard of care

Drug

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

Primary outcomes

  1. 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.

  2. Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery

    Time frame: 24 months

  3. 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

Secondary outcomes

  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries

    Time frame: 24 months

  10. 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

  11. Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index

    Time frame: From randomization up to approximately 6 years

  12. 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

  13. Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio

    Time frame: From randomization up to approximately 6 years

  14. 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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: CANTOS

Important dates

Study start
2011
Primary completion
2017
Study completion
2019
First posted
Apr 4, 2011
Registry last updated
Jan 22, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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