Anakinra to Prevent Post-infarction Remodeling

Study Overview
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Brief Summary
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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.

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

Conditions
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ST Segment Elevation Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Anakinra
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>Anakinra 100 mg given daily by subcutaneous injection for 14 days | Drug: Anakinra<br>* 100 mg daily subcutaneous injection for 14 days<br>* Other names: Kineret (TM);|
| Placebo Comparator: Placebo<br>0.67 ml of NaCl 0.9% solution | Drug: Placebo<br>* 0.67 ml of NaCl 0.9% subcutaneously daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. |  | 10-14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute myocardial infarction