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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01327846




Registration number
NCT01327846
Ethics application status
Date submitted
29/03/2011
Date registered
4/04/2011
Date last updated
22/01/2020

Titles & IDs
Public title
Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)
Scientific 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
Secondary ID [1] 0 0
2010-022970-14
Secondary ID [2] 0 0
CACZ885M2301
Universal Trial Number (UTN)
Trial acronym
CANTOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atherosclerosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard of care

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

Experimental: Canakinumab Dose 150 mg - Pivotal Phase:

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

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

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


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Analysis of Core Phase First CEC Confirmed Major Adverse Cardiovascular Events (MACE) and Its Components
Timepoint [1] 0 0
From randomization, to end of treatment plus 30 days, up to approximately 6 years
Primary outcome [2] 0 0
Substudy 1 (Core Phase): Change From Baseline in Carotid Plaque Burden in the Bifurcation Region of the Index Carotid Artery
Timepoint [2] 0 0
24 months
Primary outcome [3] 0 0
Substudy 2 (Core Phase): Change From Baseline of the Insulin Secretion Rate (ISR) Relative to Glucose 0-30 Min Defined as F30 = AUCISR 0-30 / AUCGluc 0-30 Averaged Across the Year 3, 4, 5 Visits
Timepoint [3] 0 0
From randomization up to approximately 6 years
Secondary outcome [1] 0 0
Patients With Core Phase CEC Confirmed CV Death, Non-fatal MI, Non-fatal Stroke, or Hospitalization for Unstable Angina Requiring Unplanned Revascularization
Timepoint [1] 0 0
From randomization, to end of treatment pus 30 days, up to approximately 6 years
Secondary outcome [2] 0 0
Patients With Core Phase New Onset Type 2 Diabetes Among Patients With Pre-diabetes at Randomization
Timepoint [2] 0 0
From randomization up to approximately 6 years
Secondary outcome [3] 0 0
Core Phase All-cause Mortality, Non-fatal MI, or Non-fatal Stroke
Timepoint [3] 0 0
From randomization, to end of treatment plus 30 days, up to approximately 6 years
Secondary outcome [4] 0 0
Core Phase All-cause Mortality
Timepoint [4] 0 0
From randomization, to end of treatment plus 30 days, up to approximately 6 years
Secondary outcome [5] 0 0
Summary of Adverse Events (Core Phase)
Timepoint [5] 0 0
From randomization, to end of treatment plus 30 days, up to approximately 6 years
Secondary outcome [6] 0 0
Summary of Adverse Events (Extension Phase)
Timepoint [6] 0 0
From start of Extension phase, to end of treatment plus 30 days, up to approximately 2 years
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
3 months
Secondary outcome [8] 0 0
Substudy 1 (Core Phase): Mean Total Vessel Wall Area Across the Left and Right Carotid Artery at Month 3 and Month 24
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Substudy 1 (Core Phase): Change From Baseline in Corresponding Total Vessel Wall Area in the Left and Right Carotid Arteries
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Substudy 2 (Core Phase): Change From Baseline in Insulin Sensitivity Index
Timepoint [11] 0 0
From randomization up to approximately 6 years
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
From randomization up to approximately 6 years
Secondary outcome [13] 0 0
Substudy 2 (Core Phase): Change From Baseline in Fasting Pro-Insulin Concentration/Insulin Concentration Ratio
Timepoint [13] 0 0
From randomization up to approximately 6 years
Secondary outcome [14] 0 0
Substudy 2 (Core Phase): Change From Baseline in OGTT Stimulated Area Under the Curve (AUC) 0-120 Min of C-peptide Concentration
Timepoint [14] 0 0
From randomization up to approximately 6 years

Eligibility
Key inclusion criteria
Main Study

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/04/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/04/2019
Sample size
Target
Accrual to date
Final
10066
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,TAS,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Garran
Recruitment hospital [2] 0 0
Novartis Investigative Site - Gosford
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Novartis Investigative Site - Kogarah
Recruitment hospital [4] 0 0
Novartis Investigative Site - Liverpool
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Novartis Investigative Site - Milton
Recruitment hospital [6] 0 0
Novartis Investigative Site - Southport
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Novartis Investigative Site - Hobart
Recruitment hospital [8] 0 0
Novartis Investigative Site - Bundoora
Recruitment hospital [9] 0 0
Novartis Investigative Site - Geelong
Recruitment hospital [10] 0 0
Novartis Investigative Site - Bateman
Recruitment hospital [11] 0 0
Novartis Investigative Site - Joondalup
Recruitment hospital [12] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
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2170 - Liverpool
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4064 - Milton
Recruitment postcode(s) [6] 0 0
4215 - Southport
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7000 - Hobart
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3083 - Bundoora
Recruitment postcode(s) [9] 0 0
3220 - Geelong
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6150 - Bateman
Recruitment postcode(s) [11] 0 0
6027 - Joondalup
Recruitment postcode(s) [12] 0 0
6000 - Perth
Recruitment outside Australia
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Germany
State/province [184] 0 0
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Germany
State/province [185] 0 0
Fulda
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Germany
State/province [186] 0 0
Giengen
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Germany
State/province [187] 0 0
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Country [188] 0 0
Germany
State/province [188] 0 0
Haag
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Germany
State/province [189] 0 0
Halle Saale
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Germany
State/province [190] 0 0
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Germany
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Heidelberg
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Germany
State/province [192] 0 0
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Germany
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Huy / OT Anderbeck
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Germany
State/province [194] 0 0
Jerichow
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Germany
State/province [195] 0 0
Kallstadt
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Germany
State/province [196] 0 0
Kamp-Lintfort
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Germany
State/province [197] 0 0
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Country [198] 0 0
Germany
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Kiel
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Germany
State/province [199] 0 0
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Germany
State/province [200] 0 0
Koeln
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Germany
State/province [201] 0 0
Kuenzing
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Germany
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Leipzig
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Germany
State/province [203] 0 0
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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
State/province [209] 0 0
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Germany
State/province [210] 0 0
Muehldorf Am Inn
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Germany
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Muehlhausen
Country [212] 0 0
Germany
State/province [212] 0 0
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Country [213] 0 0
Germany
State/province [213] 0 0
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Country [214] 0 0
Germany
State/province [214] 0 0
Northeim
Country [215] 0 0
Germany
State/province [215] 0 0
Nurnberg
Country [216] 0 0
Germany
State/province [216] 0 0
Oelde
Country [217] 0 0
Germany
State/province [217] 0 0
Oschatz
Country [218] 0 0
Germany
State/province [218] 0 0
Paderborn
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Germany
State/province [219] 0 0
Potsdam
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Germany
State/province [220] 0 0
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Country [221] 0 0
Germany
State/province [221] 0 0
Reinfeld
Country [222] 0 0
Germany
State/province [222] 0 0
Rostock
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Germany
State/province [223] 0 0
Rüdersdorf
Country [224] 0 0
Germany
State/province [224] 0 0
Siegen
Country [225] 0 0
Germany
State/province [225] 0 0
Ulm
Country [226] 0 0
Germany
State/province [226] 0 0
Wolmirstedt
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GR
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Athens
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Chalkida
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Greece
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Crete Heraklion
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Greece
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Patras
Country [233] 0 0
Guatemala
State/province [233] 0 0
Guatemala City
Country [234] 0 0
Guatemala
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Guatemala
Country [235] 0 0
Hungary
State/province [235] 0 0
Zala
Country [236] 0 0
Hungary
State/province [236] 0 0
Budapest
Country [237] 0 0
Hungary
State/province [237] 0 0
Csongrad
Country [238] 0 0
Hungary
State/province [238] 0 0
Debrecen
Country [239] 0 0
Hungary
State/province [239] 0 0
Gyula
Country [240] 0 0
Hungary
State/province [240] 0 0
Kistarcsa
Country [241] 0 0
Hungary
State/province [241] 0 0
Komarom
Country [242] 0 0
Hungary
State/province [242] 0 0
Miskolc
Country [243] 0 0
Hungary
State/province [243] 0 0
Mosonmagyarovar
Country [244] 0 0
Hungary
State/province [244] 0 0
Nyiregyháza
Country [245] 0 0
Hungary
State/province [245] 0 0
Pecs
Country [246] 0 0
Hungary
State/province [246] 0 0
Szeged
Country [247] 0 0
Hungary
State/province [247] 0 0
Szekesfehervar
Country [248] 0 0
Hungary
State/province [248] 0 0
Szentes
Country [249] 0 0
Iceland
State/province [249] 0 0
Kopavogur
Country [250] 0 0
Iceland
State/province [250] 0 0
Reykjavik
Country [251] 0 0
India
State/province [251] 0 0
Andhra Pradesh
Country [252] 0 0
India
State/province [252] 0 0
Andhrapradesh
Country [253] 0 0
India
State/province [253] 0 0
Delhi
Country [254] 0 0
India
State/province [254] 0 0
Gujarat
Country [255] 0 0
India
State/province [255] 0 0
Karnataka
Country [256] 0 0
India
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Kerala
Country [257] 0 0
India
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Maharashtra
Country [258] 0 0
India
State/province [258] 0 0
Punjab
Country [259] 0 0
India
State/province [259] 0 0
Rajasthan
Country [260] 0 0
India
State/province [260] 0 0
Tamil Nadu
Country [261] 0 0
India
State/province [261] 0 0
Tamil NADU
Country [262] 0 0
India
State/province [262] 0 0
Tamilnadu
Country [263] 0 0
India
State/province [263] 0 0
Telangana
Country [264] 0 0
India
State/province [264] 0 0
Uttar Pradesh
Country [265] 0 0
India
State/province [265] 0 0
Ahmedabad
Country [266] 0 0
Italy
State/province [266] 0 0
AN
Country [267] 0 0
Italy
State/province [267] 0 0
AP
Country [268] 0 0
Italy
State/province [268] 0 0
AR
Country [269] 0 0
Italy
State/province [269] 0 0
BG
Country [270] 0 0
Italy
State/province [270] 0 0
BS
Country [271] 0 0
Italy
State/province [271] 0 0
CA
Country [272] 0 0
Italy
State/province [272] 0 0
CE
Country [273] 0 0
Italy
State/province [273] 0 0
CH
Country [274] 0 0
Italy
State/province [274] 0 0
CZ
Country [275] 0 0
Italy
State/province [275] 0 0
FE
Country [276] 0 0
Italy
State/province [276] 0 0
FG
Country [277] 0 0
Italy
State/province [277] 0 0
FI
Country [278] 0 0
Italy
State/province [278] 0 0
IS
Country [279] 0 0
Italy
State/province [279] 0 0
MI
Country [280] 0 0
Italy
State/province [280] 0 0
MS
Country [281] 0 0
Italy
State/province [281] 0 0
PA
Country [282] 0 0
Italy
State/province [282] 0 0
PC
Country [283] 0 0
Italy
State/province [283] 0 0
PI
Country [284] 0 0
Italy
State/province [284] 0 0
PR
Country [285] 0 0
Italy
State/province [285] 0 0
PV
Country [286] 0 0
Italy
State/province [286] 0 0
RM
Country [287] 0 0
Italy
State/province [287] 0 0
SS
Country [288] 0 0
Italy
State/province [288] 0 0
UD
Country [289] 0 0
Italy
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VR
Country [290] 0 0
Italy
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VV
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Italy
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Napoli
Country [292] 0 0
Italy
State/province [292] 0 0
Novara
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Italy
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Veruno
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Japan
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Aichi
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Japan
State/province [295] 0 0
Chiba
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Japan
State/province [296] 0 0
Fukuoka
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Japan
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Gifu
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Japan
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Gunma
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Japan
State/province [299] 0 0
Hiroshima
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Japan
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Hyogo
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Japan
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Ibaraki
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Japan
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Kagawa
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Japan
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Japan
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Japan
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Japan
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Japan
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Nagano
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Japan
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Japan
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Japan
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Shiga
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Japan
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Japan
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Korea, Republic of
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Gangwon-Do
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Korea, Republic of
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Korea, Republic of
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Korea
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Korea, Republic of
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Korea, Republic of
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Korea, Republic of
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Korea, Republic of
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LV
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Riga
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Valmiera
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LTU
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Lithuania
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Kaunas
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Lithuania
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Lithuania
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Panevezys
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Mexico
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Mexico
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Mexico
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Mexico
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Mexico
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Mexico
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AZ
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DZ
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Netherlands
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Netherlands
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Netherlands
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Netherlands
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Deventer
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Netherlands
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Ede
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Gouda
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Netherlands
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Groningen
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Netherlands
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Haarlem
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Netherlands
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Netherlands
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Hoorn
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Netherlands
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Leeuwarden
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Netherlands
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Meppel
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Netherlands
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Netherlands
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Tiel
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Utrecht
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Netherlands
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Alesund
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Elverum
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Hamar
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Harstad
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Hønefoss
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Lillehammer
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Moss
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Nesttun
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Norway
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Oslo
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Sandefjord
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Norway
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Norway
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Stavanger
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Norway
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Tonsberg
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Trondheim
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Norway
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Lima
Country [377] 0 0
Poland
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Gdansk
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Poland
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Gdynia
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Poland
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Lublin
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Poland
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Olawa
Country [381] 0 0
Poland
State/province [381] 0 0
Ostrow Wielkopolski
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Poland
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Poznan
Country [383] 0 0
Poland
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Pulawy
Country [384] 0 0
Poland
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Rumia
Country [385] 0 0
Poland
State/province [385] 0 0
Skierniewice
Country [386] 0 0
Poland
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Torun
Country [387] 0 0
Poland
State/province [387] 0 0
Warszawa
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Poland
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Wegrow
Country [389] 0 0
Poland
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Wloclawek
Country [390] 0 0
Puerto Rico
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Manati
Country [391] 0 0
Puerto Rico
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Mayaguez
Country [392] 0 0
Puerto Rico
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Ponce
Country [393] 0 0
Puerto Rico
State/province [393] 0 0
San Juan
Country [394] 0 0
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Country [395] 0 0
Romania
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Romania
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Romania
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Romania
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Jud Bihor
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Romania
State/province [399] 0 0
Jud Cluj
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Romania
State/province [400] 0 0
Jud Iasi
Country [401] 0 0
Romania
State/province [401] 0 0
Jud Mures
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Romania
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Jud. Constanta
Country [403] 0 0
Romania
State/province [403] 0 0
Jud. Dolj
Country [404] 0 0
Romania
State/province [404] 0 0
Jud. Iasi
Country [405] 0 0
Romania
State/province [405] 0 0
Mures
Country [406] 0 0
Romania
State/province [406] 0 0
ROM
Country [407] 0 0
Romania
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Timis
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Romania
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Baia Mare
Country [409] 0 0
Romania
State/province [409] 0 0
Brasov
Country [410] 0 0
Romania
State/province [410] 0 0
Bucharest
Country [411] 0 0
Romania
State/province [411] 0 0
Bucuresti
Country [412] 0 0
Romania
State/province [412] 0 0
Cluj Napoca
Country [413] 0 0
Romania
State/province [413] 0 0
Cluj-Napoca
Country [414] 0 0
Romania
State/province [414] 0 0
Craiova
Country [415] 0 0
Romania
State/province [415] 0 0
Oradea
Country [416] 0 0
Romania
State/province [416] 0 0
Pitesti
Country [417] 0 0
Romania
State/province [417] 0 0
Sibiu
Country [418] 0 0
Romania
State/province [418] 0 0
Targu Mures
Country [419] 0 0
Romania
State/province [419] 0 0
Targu-Mures
Country [420] 0 0
Romania
State/province [420] 0 0
Timisoara
Country [421] 0 0
Russian Federation
State/province [421] 0 0
Chelyabinsk
Country [422] 0 0
Russian Federation
State/province [422] 0 0
Ekaterinburg
Country [423] 0 0
Russian Federation
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Izhevsk
Country [424] 0 0
Russian Federation
State/province [424] 0 0
Kazan
Country [425] 0 0
Russian Federation
State/province [425] 0 0
Kemerovo
Country [426] 0 0
Russian Federation
State/province [426] 0 0
Kirov
Country [427] 0 0
Russian Federation
State/province [427] 0 0
Krasnodar
Country [428] 0 0
Russian Federation
State/province [428] 0 0
Moscow
Country [429] 0 0
Russian Federation
State/province [429] 0 0
Novosibirsk
Country [430] 0 0
Russian Federation
State/province [430] 0 0
Penza
Country [431] 0 0
Russian Federation
State/province [431] 0 0
Perm
Country [432] 0 0
Russian Federation
State/province [432] 0 0
Petrozavodsk
Country [433] 0 0
Russian Federation
State/province [433] 0 0
Ryazan
Country [434] 0 0
Russian Federation
State/province [434] 0 0
Saint Petersburg
Country [435] 0 0
Russian Federation
State/province [435] 0 0
Saint-Petersburg
Country [436] 0 0
Russian Federation
State/province [436] 0 0
Samara
Country [437] 0 0
Russian Federation
State/province [437] 0 0
Saratov
Country [438] 0 0
Russian Federation
State/province [438] 0 0
Sestroretsk
Country [439] 0 0
Russian Federation
State/province [439] 0 0
Smolensk
Country [440] 0 0
Russian Federation
State/province [440] 0 0
St-Petersburg
Country [441] 0 0
Russian Federation
State/province [441] 0 0
St. Petersburg
Country [442] 0 0
Russian Federation
State/province [442] 0 0
St.- Petersburg
Country [443] 0 0
Russian Federation
State/province [443] 0 0
St.Petersburg
Country [444] 0 0
Russian Federation
State/province [444] 0 0
Syktyvkar
Country [445] 0 0
Russian Federation
State/province [445] 0 0
Tomsk
Country [446] 0 0
Russian Federation
State/province [446] 0 0
Tyumen
Country [447] 0 0
Russian Federation
State/province [447] 0 0
Vladimir
Country [448] 0 0
Russian Federation
State/province [448] 0 0
Yaroslavl
Country [449] 0 0
Russian Federation
State/province [449] 0 0
Yekaterinburg
Country [450] 0 0
Serbia
State/province [450] 0 0
Beograd
Country [451] 0 0
Serbia
State/province [451] 0 0
Niska Banja
Country [452] 0 0
Serbia
State/province [452] 0 0
Nis
Country [453] 0 0
Serbia
State/province [453] 0 0
Sremska Kamenica
Country [454] 0 0
Slovakia
State/province [454] 0 0
Slovak Republic
Country [455] 0 0
Slovakia
State/province [455] 0 0
Banska Bystrica
Country [456] 0 0
Slovakia
State/province [456] 0 0
Bardejov
Country [457] 0 0
Slovakia
State/province [457] 0 0
Bratislava
Country [458] 0 0
Slovakia
State/province [458] 0 0
Dubnica nad Vahom
Country [459] 0 0
Slovakia
State/province [459] 0 0
Dunajska Streda
Country [460] 0 0
Slovakia
State/province [460] 0 0
Galanta
Country [461] 0 0
Slovakia
State/province [461] 0 0
Kosice
Country [462] 0 0
Slovakia
State/province [462] 0 0
Levice
Country [463] 0 0
Slovakia
State/province [463] 0 0
Lucenec
Country [464] 0 0
Slovakia
State/province [464] 0 0
Martin
Country [465] 0 0
Slovakia
State/province [465] 0 0
Nitra
Country [466] 0 0
Slovakia
State/province [466] 0 0
Nove Zamky
Country [467] 0 0
Slovakia
State/province [467] 0 0
Presov
Country [468] 0 0
Slovakia
State/province [468] 0 0
Trnava
Country [469] 0 0
Slovakia
State/province [469] 0 0
Zilina
Country [470] 0 0
Slovenia
State/province [470] 0 0
Celje
Country [471] 0 0
Slovenia
State/province [471] 0 0
Golnik
Country [472] 0 0
Slovenia
State/province [472] 0 0
Ljubljana
Country [473] 0 0
South Africa
State/province [473] 0 0
Kwa-Zulu Natal
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01327846
Trial related presentations / publications
Ridker PM, Tuttle KR, Perkovic V, Libby P, MacFadyen JG. Inflammation drives residual risk in chronic kidney disease: a CANTOS substudy. Eur Heart J. 2022 Dec 7;43(46):4832-4844. doi: 10.1093/eurheartj/ehac444.
Svensson EC, Madar A, Campbell CD, He Y, Sultan M, Healey ML, Xu H, D'Aco K, Fernandez A, Wache-Mainier C, Libby P, Ridker PM, Beste MT, Basson CT. TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial. JAMA Cardiol. 2022 May 1;7(5):521-528. doi: 10.1001/jamacardio.2022.0386.
Everett BM, MacFadyen JG, Thuren T, Libby P, Glynn RJ, Ridker PM. Inhibition of Interleukin-1beta and Reduction in Atherothrombotic Cardiovascular Events in the CANTOS Trial. J Am Coll Cardiol. 2020 Oct 6;76(14):1660-1670. doi: 10.1016/j.jacc.2020.08.011.
Schieker M, Conaghan PG, Mindeholm L, Praestgaard J, Solomon DH, Scotti C, Gram H, Thuren T, Roubenoff R, Ridker PM. Effects of Interleukin-1beta Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2020 Oct 6;173(7):509-515. doi: 10.7326/M20-0527. Epub 2020 Aug 4.
Vallurupalli M, MacFadyen JG, Glynn RJ, Thuren T, Libby P, Berliner N, Ridker PM. Effects of Interleukin-1beta Inhibition on Incident Anemia: Exploratory Analyses From a Randomized Trial. Ann Intern Med. 2020 Apr 21;172(8):523-532. doi: 10.7326/M19-2945. Epub 2020 Mar 24. Erratum In: Ann Intern Med. 2020 Aug 18;173(4):324. doi: 10.7326/L20-0934.
Rothman AM, MacFadyen J, Thuren T, Webb A, Harrison DG, Guzik TJ, Libby P, Glynn RJ, Ridker PM. Effects of Interleukin-1beta Inhibition on Blood Pressure, Incident Hypertension, and Residual Inflammatory Risk: A Secondary Analysis of CANTOS. Hypertension. 2020 Feb;75(2):477-482. doi: 10.1161/HYPERTENSIONAHA.119.13642. Epub 2019 Dec 30.
Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1beta inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2020 Jun 14;41(23):2153-2163. doi: 10.1093/eurheartj/ehz542.
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-1beta 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-1beta 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-1beta 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-1beta 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.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01327846