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)

Virginia Commonwealth University (VCU)

Status: Completed

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

Treatments: Other: Echocardiogram; Other: Cardiopulmonary exercise test

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01900600

20110521 (Other Identifier)

HM13782

Details and patient eligibility

About

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.

Full description

Patients enrolled in the CANTOS trial (with prior acute myocardial infarction [>30 days] and elevated C reactive protein levels [CRP>2mg/l]) who also have reduced left ventricular ejection fraction (LVEF<50%) and are symptomatic for heart failure (New York Heart Association symptoms class II-III) will be offered to take part in this sub-study at the Virginia Commonwealth University site.

As part of the sub-study, patients will undergo a cardiopulmonary exercise test (CPX) at baseline prior to initiation of treatment, then repeated at 3 and 12 months, and a transthoracic echocardiogram at baseline and at 12 months.

Enrollment: 15 patients

Sex: All

Ages: 18 to 110 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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15 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Cardiopulmonary exercise test

Other: Echocardiogram

Canakinumab 50 mg quarterly

Active Comparator group

Description:

Canakinumab 50 mg quarterly

Treatment:

Other: Cardiopulmonary exercise test

Other: Echocardiogram

Canakinumab 150 mg quarterly

Active Comparator group

Description:

Canakinumab 150 mg quarterly

Treatment:

Other: Cardiopulmonary exercise test

Other: Echocardiogram

Canakinumab 300 mg quarterly

Active Comparator group

Description:

Canakinumab 300 mg quarterly

Treatment:

Other: Cardiopulmonary exercise test

Other: Echocardiogram