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

This study is currently recruiting participants.
Verified November 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT01327846
First Posted: April 4, 2011
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose

Main Study (CACZ885M2301): The purpose of the pivotal phase 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.

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 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
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

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 ]
  • Substudy 1; Change from baseline in carotid plaque burden in the bifurcation region of the index carotid artery [ Time Frame: 36 months ]
  • 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 ]

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 ]
  • Main:Time to new onset type 2 diabetes among patients with pre-diabetes at randomization. [ Time Frame: 36 months ]
  • Main:Time to first occurrence of non-fatal MI, stroke and all-cause mortality composite. [ Time Frame: 36 months ]
  • Main: Time to all-cause mortality. [ Time Frame: 36 months ]
  • Substudy 1; Change from baseline of the total vessel wall area at Month 3 of the index carotid artery. [ Time Frame: 36 months ]
  • Substudy 1; Mean total vessel wall area across the left and right carotid artery at Month 3 and Month 24. [ Time Frame: 36 months ]
  • Substudy 1; Change from baseline in corresponding total vessel wall area in the left and right carotid arteries. [ Time Frame: 36 months ]
  • 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 ]
  • Substudy 2; Change from baseline in insulin sensitivity index. [ Time Frame: 36 months ]
  • 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 ]
  • Substudy 2; Change from baseline in fasting pro-insulin concentration /insulin concentration ratio. [ Time Frame: 36 months ]
  • Substudy 2; Change from baseline in OGTT stimulated area under the curve (AUC) 0-120 min of C-peptide concentration. [ Time Frame: 36 months ]

Estimated Enrollment: 10000
Actual Study Start Date: April 11, 2011
Estimated Study Completion Date: December 2, 2019
Primary Completion Date: March 28, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab Dose 50 mg

Pivotal Phase:

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

Extension Phase:

Blinded canakinumab 50 mg quarterly subcutaneous + standard of care therapy, switched to open-label canakinumab 150 mg quarterly subcutaneous + standard of care therapy after 9 months.

Drug: Canakinumab
Experimental: Canakinumab Dose 150 mg

Pivotal Phase:

Blinded Canakinumab 150 mg quarterly subcutaneous + standard of care therapy.

Extension Phase:

Blinded canakinumab 150 mg quarterly subcutaneous + standard of care therapy, switched to open-label canakinumab 150 mg quarterly subcutaneous + standard of care therapy after 9 months.

Drug: Canakinumab
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:

Blinded canakinumab 300 mg quarterly subcutaneous + standard of care therapy, switched to open-label canakinumab 150 mg quarterly subcutaneous + standard of care therapy after 9 months.

Drug: Canakinumab
Placebo Comparator: Placebo

Pivotal Phase:

Blinded matching placebo quarterly subcutaneous + standard of care therapy.

Extension Phase:

Blinded matching placebo quarterly subcutaneous + standard of care therapy, switched to open-label canakinumab 150 mg quarterly subcutaneous + standard of care therapy after 9 months.

Drug: Placebo

Detailed Description:
There will be a seamless transition from the pivotal phase to the extension phase of the main study. LPLV of the pivotal phase will be in 02/2017.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01327846


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 trialandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 trialandresults.registries@novartis.com

  Show 1355 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01327846     History of Changes
Other Study ID Numbers: CACZ885M2301
2010-022970-14 ( EudraCT Number )
First Submitted: March 29, 2011
First Posted: April 4, 2011
Last Update Posted: November 17, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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

Additional relevant MeSH terms:
Myocardial Infarction
Heart Diseases
Atherosclerosis
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs