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)

October 9, 2018 updated by: Virginia Commonwealth University

Substudy of the the CANTOS Trial (Interleukin-1 Blockade With Canakinumab to Improve Exercise Capacity in Patients With Chronic Systolic Heart Failure and Elevated Hs-CRP; CACZ885M2301)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 110 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Other: Cardiopulmonary 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.
Other Names:
  • Cardiopulmonary exercise test (CPX)
Other: Echocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.
Other Names:
  • Echocardiogram or Echo
ACTIVE_COMPARATOR: Canakinumab 50 mg quarterly
Other: Cardiopulmonary 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.
Other Names:
  • Cardiopulmonary exercise test (CPX)
Other: Echocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.
Other Names:
  • Echocardiogram or Echo
ACTIVE_COMPARATOR: Canakinumab 150 mg quarterly
Other: Cardiopulmonary 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.
Other Names:
  • Cardiopulmonary exercise test (CPX)
Other: Echocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.
Other Names:
  • Echocardiogram or Echo
ACTIVE_COMPARATOR: Canakinumab 300 mg quarterly
Other: Cardiopulmonary 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.
Other Names:
  • Cardiopulmonary exercise test (CPX)
Other: Echocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 12 months later.
Other Names:
  • Echocardiogram or Echo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak oxygen consumption (VO2)
Time Frame: 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).
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak VO2 change
Time Frame: 12 months
Difference in the interval changes from baseline and 12 months in peak VO2 comparing CANAKINUMAB (all doses) with placebo
12 months
Ventilatory efficiency (VE/VCO2 slope) change
Time Frame: 12 months
Difference in the interval changes from baseline and 3 months in the VE/VCO2 slope comparing CANAKINUMAB (all doses) with placebo
12 months
OUES
Time Frame: 12 months
Difference in the interval changes from baseline and 12 months in oxygen utilization efficiency slope (OUES) comparing CANAKINUMAB (all doses) with placebo
12 months
LVEF change
Time Frame: 12 months
Difference in the interval changes from baseline and 12 months in left ventricular ejection fraction (LVEF) comparing CANAKINUMAB (all doses) with placebo
12 months
Diastolic function change
Time Frame: 12 months
Difference in the interval changes from baseline and 12 months in E/E' (diastolic function) comparing CANAKINUMAB (all doses) with placebo
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (ACTUAL)

January 8, 2015

Study Completion (ACTUAL)

January 8, 2015

Study Registration Dates

First Submitted

July 6, 2013

First Submitted That Met QC Criteria

July 11, 2013

First Posted (ESTIMATE)

July 16, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 10, 2018

Last Update Submitted That Met QC Criteria

October 9, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM13782
  • 20110521 (OTHER: WIRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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