Anakinra to Prevent Post-infarction Remodeling (VCU-ART)

October 24, 2017 updated by: Virginia Commonwealth University

Recombinant Human Interleukin-1 Receptor Antagonist, Anakinra, to Prevent Post-infarction Remodeling: the Virginia Commonwealth University Anakinra Remodeling Trial (VCU-ART)

Thousands of patients die daily from early and late complications of a heart attack (acute myocardial infarction, AMI). Patients surviving AMI remain at high risk of death from adverse cardiac remodeling (dysfunction and enlargement of the heart) leading to heart failure (weakening of the heart).

Current interventions proven to reduce adverse remodeling and progression to heart failure include early reperfusion (restoring blood flow to the heart muscle) and long-term use of medicines that block the effects of hormones (such as angiotensin II, norepinephrine and aldosterone) involved in adverse remodeling. Despite these treatments, however, many patients continue to develop heart failure within 1 year of AMI. These patients are at very high risk of death.

Numerous changes occur in the hearts of patients after AMI that lead to adverse remodeling. Ischemia (lack of oxygen) and infarction (cell damage) lead to increased interleukin-1 (IL-1) production in the heart. IL-1 plays a critical role in adverse cardiac remodeling by coordinating the inflammatory pathway (leading to wound healing) and apoptotic pathway (leading to cell death).

In opposition to IL-1 activity, the human body produces a natural IL-1 receptor antagonist that blocks the effects of IL-1. The drug form of this IL-1 receptor antagonist (anakinra) is currently FDA approved for the treatment of rheumatoid arthritis, an inflammatory disease characterized by excessive IL-1 activity. Experimental studies show that anakinra is able to prevent cardiac remodeling and improve survival in mice after AMI.

We hypothesize that anakinra will show similar benefits in human patients by preventing adverse remodeling and heart failure after AMI.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 3

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >18 years
  • Acute (<24 hours) onset of chest pain
  • New or presumably new ST elevation on ECG
  • Planned coronary angiography for percutaneous revascularization

Exclusion Criteria:

  • Inability to give informed consent
  • Late presentation (>24 hours)
  • Unsuccessful revascularization or urgent coronary bypass surgery
  • Hemodynamic instability
  • End-stage congestive heart failure (AHA/ACC stage C/D, NYHA class IV)
  • Preexisting severe LV dysfunction (LVEF<20%) or severe valvular disease
  • Severe asthma
  • Pregnancy ( pre-enrollment pregnancy test)
  • Contraindications to cardiac MRI or cardiac angiography
  • Severe coagulopathy (INR>2.0, Platelet count<50,000/mm3)
  • Severe renal insufficiency (creatinine clearance <30 ml/min/m2)
  • Recent (<14 days) use of anti-inflammatory drugs (NSAIDS excluded)
  • Chronic inflammatory 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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra
Anakinra 100 mg given daily by subcutaneous injection for 14 days
Drug: Anakinra
100 mg daily subcutaneous injection for 14 days
Other Names:
  • Kineret (TM)
Placebo Comparator: Placebo
0.67 ml of NaCl 0.9% solution
Drug: Placebo
0.67 ml of NaCl 0.9% subcutaneously daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference Between the Anakinra Arm and Placebo Arm in Change in End-systolic Volume Indices From Baseline to Follow up Exam 10-14 Weeks Later at Cardiac Magnetic Resonance Imaging.
Time Frame: 10-14 weeks
10-14 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Difference Between the 2 Arms in the Percentage of Patients With Any of the Following : a) End-systolic or End-diastolic Volume Index Increase >10%; b) Ejection Fraction Decrease >10%; c) E/E'>15 at Follow up
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in Change in the Number of Circulating Endothelial Progenitor Cells From Baseline to Follow up Exam
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in Change in Serum BNP Levels, C-reactive Protein, and Hemoglobin A1c% From Baseline to Follow up
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in the Incidence of Significant Cardiac Arrhythmias in the Acute Phase
Time Frame: 48 hours
48 hours
Difference Between the 2 Arms in the Number of Adverse Effects Including a) All Events; b) All Events Requiring Unblinding of the Treatment; c) All Events Requiring Early Termination of the Intervention
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in Change in Oxygen Uptake Kinetics From Baseline to Follow up Exam at Submaximal Cardiopulmonary Exercise Test
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in Change in E/E' Ratios and Myocardial Performance (Tei) Indices From Baseline to Follow up Exam at Transthoracic Echo-color-Doppler Cardiac Exam
Time Frame: 10-14 weeks
10-14 weeks
Difference Between the 2 Arms in Change in End-diastolic Volume Indices and Ejection Fraction Values From Baseline to Follow up Exam at Cardiac Magnetic Resonance Imaging
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

Investigators

  • Principal Investigator: Antonio Abbate, MD, 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

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

November 1, 2008

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

November 11, 2008

First Submitted That Met QC Criteria

November 12, 2008

First Posted (Estimate)

November 13, 2008

Study Record Updates

Last Update Posted (Actual)

November 30, 2017

Last Update Submitted That Met QC Criteria

October 24, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VCU-ART

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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