Interleukin-1 Blockade With Canakinumab to Improve Exercise Capacity in Patients With Chronic Systolic Heart Failure and Elevated High Sensitivity C-reactive Protein (Hs-CRP)

NCT01900600 | Completed

• 2 other identifiers: HM1378220110521
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a sub-study of the CANTOS trial (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 high sensitivity C-reaction protein (hsCRP) \[CACZ885M2301\]). The study proposes to perform serial Cardiopulmonary Exercise Tests (CPX) to prospectively measure changes in aerobic exercise capacity in patients with prior myocardial infarction (MI), elevated C reactive protein plasma levels, and symptomatic heart failure with reduced systolic function, who are enrolled in the main CANTOS trial and are randomly assigned to Canakinumab (3 different doses) or Placebo. The subjects enrolled in this substudy will undergo repeated CPX and echocardiograms over the first 12 months of the CANTOS trial. The subjects will received the experimental treatment as randomized in the main CANTOS trial and they will not receive any additional experimental treatment as part of the sub-study. This study is a an Investigator-initiated (Dr. Abbate) single-center (Virginia Commonwealth University) sub-study of the CANTOS trial, supported by Novartis pharmaceuticals.

Conditions

Prior Acute Myocardial Infarction; Evidence of Systemic Inflammation (C Reactive Protein Plasma >2 mg/l); Reduced Left Ventricle Ejection Fraction (<50%); Symptoms of Heart Failure (NYHA Class II-III)

Outcome Measures

Primary Outcomes (1)

• Peak oxygen consumption (VO2)

  Difference in the interval change from baseline in peak VO2 at 3 months following a single dose of CANAKINUMAB 50 mg subcutaneous, 150 mg subcutaneous, or CANAKINUMAB 300 mg subcutaneous \[all three groups combined\] when compared with the interval change in placebo (placebo-corrected interval change).

  3 months

Secondary Outcomes (5)

• Peak VO2 change

  12 months

• Ventilatory efficiency (VE/VCO2 slope) change

  12 months

• OUES

  12 months

• LVEF change

  12 months

• Diastolic function change

  12 months

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo

Other: Cardiopulmonary exercise test; Other: Echocardiogram

Canakinumab 50 mg quarterly

ACTIVE COMPARATOR

Canakinumab 50 mg quarterly

Other: Cardiopulmonary exercise test; Other: Echocardiogram

Canakinumab 150 mg quarterly

ACTIVE COMPARATOR

Canakinumab 150 mg quarterly

Other: Cardiopulmonary exercise test; Other: Echocardiogram

Canakinumab 300 mg quarterly

ACTIVE COMPARATOR

Canakinumab 300 mg quarterly

Other: Cardiopulmonary exercise test; Other: Echocardiogram

Interventions

Cardiopulmonary exercise test OTHER

All patients will undergo a first CPX prior to initiation of treatment, a second one after 3 months, and a third one after 12 months of treatment.

Also known as: Cardiopulmonary exercise test (CPX)

Canakinumab 150 mg quarterly; Canakinumab 300 mg quarterly; Canakinumab 50 mg quarterly; Placebo

Echocardiogram OTHER

An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.

Also known as: Echocardiogram or Echo

Canakinumab 150 mg quarterly; Canakinumab 300 mg quarterly; Canakinumab 50 mg quarterly; Placebo

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• all criteria listed in the CANTOS trial (CACZ885M2301)
• left ventricular ejection fraction \<50%
• symptoms of heart failure (NYHA class II-III)

You may not qualify if:

• all criteria listed in the CANTOS trial (CACZ885M2301)
• inability to complete a treadmill exercise test
• conditions preventing interpretation of the cardiopulmonary test (arrhythmias, ischemia, hypertension, pulmonary disease)

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (3)

• 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.

  PMID: 21982649 BACKGROUND

• Abbate A, Van Tassell BW, Biondi-Zoccai GG. Blocking interleukin-1 as a novel therapeutic strategy for secondary prevention of cardiovascular events. BioDrugs. 2012 Aug 1;26(4):217-33. doi: 10.1007/BF03261881.

  PMID: 22571369 BACKGROUND

• Trankle CR, Canada JM, Cei L, Abouzaki N, Oddi-Erdle C, Kadariya D, Christopher S, Viscusi M, Del Buono M, Kontos MC, Arena R, Van Tassell B, Abbate A. Usefulness of Canakinumab to Improve Exercise Capacity in Patients With Long-Term Systolic Heart Failure and Elevated C-Reactive Protein. Am J Cardiol. 2018 Oct 15;122(8):1366-1370. doi: 10.1016/j.amjcard.2018.07.002. Epub 2018 Jul 20.

  PMID: 30244844 DERIVED

Related Links

• Main CANTOS website

MeSH Terms

Interventions

Exercise Test; Caves

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Geological Phenomena; Physical Phenomena; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health

Study Officials

• Antonio Abbate, MD, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2013
• First Posted: July 16, 2013
• Study Start: April 1, 2013
• Primary Completion: January 8, 2015
• Study Completion: January 8, 2015
• Last Updated: October 10, 2018

Record last verified: 2018-10

Locations

US (1)