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)
Conditions
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.
Detailed 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.
Interventions
OTHERCardiopulmonary exercise test
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.
OTHEREchocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.
Sponsors
Novartis Pharmaceuticals
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak oxygen consumption (VO2) | 3 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak VO2 change | 12 months | Difference in the interval changes from baseline and 12 months in peak VO2 comparing CANAKINUMAB (all doses) with placebo |
| Ventilatory efficiency (VE/VCO2 slope) change | 12 months | Difference in the interval changes from baseline and 3 months in the VE/VCO2 slope comparing CANAKINUMAB (all doses) with placebo |
| OUES | 12 months | Difference in the interval changes from baseline and 12 months in oxygen utilization efficiency slope (OUES) comparing CANAKINUMAB (all doses) with placebo |
| LVEF change | 12 months | Difference in the interval changes from baseline and 12 months in left ventricular ejection fraction (LVEF) comparing CANAKINUMAB (all doses) with placebo |
| Diastolic function change | 12 months | Difference in the interval changes from baseline and 12 months in E/E' (diastolic function) comparing CANAKINUMAB (all doses) with placebo |
Countries
United States
Outcome results
None listed