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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01327846
First received: March 29, 2011
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

Main Study (CACZ885M2301) The purpose of this trial is to test the hypothesis that canakinumab treatment of patients with MI at least one month prior to study entry and elevated hsCRP will prevent recurrent cardiovascular events.

Sub-study 1 (CACZ885M2301S1) The purpose of this sub-study is 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 is 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 increases insulin secretion and insulin sensitivity.


Condition Intervention Phase
Atherosclerosis
Drug: Canakinumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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 Including Substudies to Evaluate the Effect of Canakinumab on Carotid Atherosclerosis, and on Glucose Control Following OGTT in T2DM

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Main:Time to first occurrence of major adverse cardiovascular event, which is a composite of CV death, non-fatal MI, and stroke. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 1; Change from baseline in carotid plaque burden in the bifurcation region of the index carotid artery [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 2; 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 yearly visits. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Main:Time to 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 ] [ Designated as safety issue: No ]
  • Main:Time to new onset type 2 diabetes among patients with pre-diabetes at randomization. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Main:Time to first occurrence of non-fatal MI, stroke and all-cause mortality composite. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Main: Time to all-cause mortality. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 1; Change from baseline of the total vessel wall area at Month 3 of the index carotid artery. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 1; Mean total vessel wall area across the left and right carotid artery at Month 3 and Month 24. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 1; Change from baseline in corresponding total vessel wall area in the left and right carotid arteries. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 1; 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: 36 months ] [ Designated as safety issue: No ]
  • Substudy 2; Change from baseline in insulin sensitivity index. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 2; 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: 36 months ] [ Designated as safety issue: No ]
  • Substudy 2; Change from baseline in fasting pro-insulin concentration /insulin concentration ratio. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Substudy 2; Change from baseline in OGTT stimulated area under the curve (AUC) 0-120 min of C-peptide concentration. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 10000
Study Start Date: April 2011
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab 50 mg
Description: Canakinumab 50 mg quarterly subcutaneous + standard of care therapy.
Drug: Canakinumab
Experimental: Canakinumab Dose 150 mg
Description: Canakinumab 150 mg quarterly subcutaneous + standard of care therapy.
Drug: Canakinumab
Experimental: Canakinumab Dose 300 mg
Description: Canakinumab 300 mg quarterly subcutaneous + standard of care therapy.
Drug: Canakinumab
Placebo Comparator: Placebo
Description: Matching placebo quarterly subcutaneous + standard of care therapy.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. Other protocol-defined inclusion/exclusion criteria may apply
  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 ClinicalTrials.gov identifier: NCT01327846

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 1562 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01327846     History of Changes
Other Study ID Numbers: CACZ885M2301, 2010-022970-14
Study First Received: March 29, 2011
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Cardiovascular Death
Myocardial Infarction
Stroke
Canakinumab
IL-1B
hsCRP

Additional relevant MeSH terms:
Atherosclerosis
Myocardial Infarction
Carotid Artery Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Myocardial Ischemia
Heart Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014