March 29, 2011
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April 4, 2011
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January 25, 2019
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April 11, 2011
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March 28, 2017 (Final data collection date for primary outcome measure)
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- 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 ]
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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 ]
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Complete list of historical versions of study NCT01327846 on ClinicalTrials.gov Archive Site
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- 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 ]
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- 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 ]
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Not Provided
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Not Provided
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Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)
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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
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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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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.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Atherosclerosis
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- 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
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- 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.
Interventions:
- Drug: Canakinumab
- Drug: Standard of care
- 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.
Interventions:
- Drug: Canakinumab
- Drug: Placebo
- 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:
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.
Interventions:
- Drug: Canakinumab
- Drug: Standard of care
- 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.
Interventions:
- Drug: Placebo
- Drug: Standard of care
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- Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2019 Sep 1. pii: ehz542. doi: 10.1093/eurheartj/ehz542. [Epub ahead of print]
- Everett BM, Cornel JH, Lainscak M, Anker SD, Abbate A, Thuren T, Libby P, Glynn RJ, Ridker PM. Anti-Inflammatory Therapy With Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation. 2019 Mar 5;139(10):1289-1299. doi: 10.1161/CIRCULATIONAHA.118.038010.
- Solomon DH, Glynn RJ, MacFadyen JG, Libby P, Thuren T, Everett BM, Ridker PM. Relationship of Interleukin-1β Blockade With Incident Gout and Serum Uric Acid Levels: Exploratory Analysis of a Randomized Controlled Trial. Ann Intern Med. 2018 Oct 16;169(8):535-542. doi: 10.7326/M18-1167. Epub 2018 Sep 18.
- Ridker PM, Libby P, MacFadyen JG, Thuren T, Ballantyne C, Fonseca F, Koenig W, Shimokawa H, Everett BM, Glynn RJ. Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J. 2018 Oct 7;39(38):3499-3507. doi: 10.1093/eurheartj/ehy310.
- Ridker PM, MacFadyen JG, Glynn RJ, Koenig W, Libby P, Everett BM, Lefkowitz M, Thuren T, Cornel JH. Inhibition of Interleukin-1β by Canakinumab and Cardiovascular Outcomes in Patients With Chronic Kidney Disease. J Am Coll Cardiol. 2018 May 29;71(21):2405-2414. doi: 10.1016/j.jacc.2018.03.490.
- Everett BM, Donath MY, Pradhan AD, Thuren T, Pais P, Nicolau JC, Glynn RJ, Libby P, Ridker PM. Anti-Inflammatory Therapy With Canakinumab for the Prevention and Management of Diabetes. J Am Coll Cardiol. 2018 May 29;71(21):2392-2401. doi: 10.1016/j.jacc.2018.03.002. Epub 2018 Mar 12.
- Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ; CANTOS Trial Group. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018 Jan 27;391(10118):319-328. doi: 10.1016/S0140-6736(17)32814-3. Epub 2017 Nov 13.
- Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ; CANTOS Trial Group. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Oct 21;390(10105):1833-1842. doi: 10.1016/S0140-6736(17)32247-X. Epub 2017 Aug 27.
- Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.
- Canada JM, Fronk DT, Cei LF, Carbone S, Erdle CO, Abouzaki NA, Melchior RD, Thomas CS, Christopher S, Turlington JS, Trankle CR, Thurber CJ, Evans RK, Dixon DL, Van Tassell BW, Arena R, Abbate A. Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure. Am J Cardiol. 2016 Jan 1;117(1):116-20. doi: 10.1016/j.amjcard.2015.10.020. Epub 2015 Oct 19.
- Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011 Oct;162(4):597-605. doi: 10.1016/j.ahj.2011.06.012. Epub 2011 Sep 14.
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Active, not recruiting
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10071
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7302
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April 1, 2020
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March 28, 2017 (Final data collection date for primary outcome measure)
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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.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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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
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Czech Republic, Ecuador, Former Serbia and Montenegro, Israel
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NCT01327846
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CACZ885M2301 2010-022970-14 ( EudraCT Number )
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Not Provided
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Undecided |
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 |
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Novartis ( Novartis Pharmaceuticals )
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Novartis Pharmaceuticals
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Not Provided
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Study Director: |
Novartis Pharmaceuticals |
Novartis Pharmaceuticals |
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Novartis
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January 2019
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