Anakinra to Prevent Adverse Post-infarction Remodeling (2) (VCU-ART2)

May 9, 2016 updated by: Virginia Commonwealth University

Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. Many patients die early during the course, and those who survive are at risk for dying late from adverse cardiac remodeling and heart failure.

The initial ischemic damage to the myocardium initiates an intense inflammatory response in promoting further cardiac dysfunction and heart failure. The investigators propose that an antiinflammatory strategy based on blockade of Interleukin-1 will quench the inflammatory response and lead to a more favorable cardiac remodeling process.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. Many patients die early during the course, and those who survive are at risk for dying late from adverse cardiac remodeling and heart failure.

The initial ischemic damage to the myocardium initiates an intense inflammatory response in promoting further cardiac dysfunction and heart failure. Interleukin-1 (IL-1) is the prototypical inflammatory cytokine involved in the tissue response to injury. In the experimental model of large anterior wall AMI in the mouse, IL-1 blockade using anakinra, a recombinant human IL-1 receptor antagonist ameliorates cardiac remodeling and improves survival following AMI. Although the mouse AMI model is helpful in understanding the events leading to adverse post-infarction cardiac remodeling and heart failure, the exact role of IL-1 in patients with AMI has not been completely characterized. The investigators propose to address this question by studying patients presenting with ST-segment elevation AMI (STEMI). Such patients are at high risk for in-hospital and long-term mortality and display several markers of inflammation. The investigators hypothesize that IL-1 blockade in patients STEMI with will limit the acute inflammatory response and prevent adverse cardiac remodeling, heart failure, and related morbidity.

The investigators hypothesize that treatment with anakinra will lead to more favorable cardiac remodeling. Left ventricular end-systolic volume index (LVESVi) is the preferred clinical marker of adverse cardiac remodeling and a strong predictor of heart failure-related mortality in patients with STEMI, and will be used as primary endpoint of the study. The investigators propose that anakinra will reduce the change in LVESVi from baseline to 10-14 weeks after STEMI, and will prevent, at least in part, other changes in cardiac function and exercise tolerance associated with adverse cardiac remodeling and heart failure.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

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:

  • Patients with STEMI will be asked to enroll according to the following inclusion criteria:

    • age > 18 years,
    • acute (<12 h) onset of chest pain associated with ST segment elevation (>2 mm) in 2 or more anatomically contiguous leads at ECG,
    • and successful primary percutaneous coronary intervention.

Exclusion criteria:

  • inability to give informed consent,
  • late presentation (>12 h),
  • unsuccessful revascularization procedure,
  • hemodynamic instability including hypotension,
  • prior Q-wave AMI,
  • end-stage congestive heart failure (American Heart Association [AHA]/American College of Cardiology [ACC] class C-D, New York Heart Association IV), severe left ventricular dysfunction (EF<20%),
  • severe valvular heart disease,
  • pregnancy, dye allergy or contraindications to cardiac angiography and/or magnetic resonance imaging, coagulopathy (INR>1.5 or platelet count<50000/mm3),
  • recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs),
  • chronic inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus), and malignancy or any comorbidity limiting survival or conditions predicting inability to complete the study.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra
Anakinra 100 mg injectable subcutaneously daily
Drug: Anakinra
Anakinra 100 mg s.c. daily for 14 days
Other Names:
  • Kineret
Placebo Comparator: Placebo
0.67 ml of sodium chloride (NaCl) 0.9% solution
Drug: Placebo
0.67 ml of NaCl 0.9% solution given subcutaneously daily for 14 days
Other Names:
  • NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular End-systolic Volume Indices
Time Frame: 10-14 weeks minus baseline
Change in n left ventricular end-systolic volume indices from baseline to follow up exam at cardiac magnetic resonance imaging comparing anakinra- and placebo-treated patients.
10-14 weeks minus baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular End-diastolic Volume Indices From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Reverse Remodeling (Reduction in LVESVi >5%)
Time Frame: 10-14 weeks
10-14 weeks
Median Difference Between the 2 Arms in the Peak Oxygen Consumption (VO2) at 10-14 Weeks
Time Frame: 10-14 weeks
10-14 weeks
Incidence of Heart Failure
Time Frame: 10-14 weeks
Difference between the anakinra arm and the placebo arm in number of patients with a new diagnosis or admission to the hospital for heart failure
10-14 weeks
Number of Adverse Events in Each Group
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arm in the Interval Change in Right Ventricular Ejection Fraction (RVEF)
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the Anakinra Arm and the Placebo Arm in Change in Left Ventricular Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging
Time Frame: 10-14 weeks
10-14 weeks
Median Difference Between the 2 Arms in the Ratio of Minute Ventilation and Carbon Dioxide Production (VE/VCO2 Slope) at 10-14 Weeks
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Reverse Remodeling (Reduction in LVESVi >10%)
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Adverse Remodeling (LVESVi Increase >5%) Based Upon Cardiac Magnetic Resonance Imaging
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Adverse Remodeling (LVESVi Increase >10%)
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Left Ventricular Ejection Fraction Change >5%
Time Frame: 10-14 weeks
10-14 weeks
Percentage of Patients in Each Group With Left Ventricular Ejection Fraction Change >10%
Time Frame: 10-14 weeks
10-14 weeks
Number of Deaths in Each Group
Time Frame: 10-14 weeks
10-14 weeks
Number of Adverse Events Requiring Withdrawal in Each Group
Time Frame: 10-14 weeks
10-14 weeks

Collaborators and Investigators

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

Sponsor

Virginia Commonwealth University

Collaborators

American Heart Association

Investigators

  • Principal Investigator: Antonio Abbate, M.D., Ph.D., Virginia Commonwealth University

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

Helpful Links

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

July 1, 2010

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

July 30, 2010

First Submitted That Met QC Criteria

August 3, 2010

First Posted (Estimate)

August 4, 2010

Study Record Updates

Last Update Posted (Estimate)

May 23, 2016

Last Update Submitted That Met QC Criteria

May 9, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHA 10SDG3030051

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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