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

Virginia Commonwealth University (VCU)

Status and phase: Completed; Phase 3

Conditions: ST Segment Elevation Acute Myocardial Infarction

Treatments: Drug: Placebo; Drug: Anakinra

Study type: Interventional

Funder types: Other

Identifiers

NCT00789724

VCU-ART

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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10 participants in 2 patient groups, including a placebo group

Anakinra

Experimental group

Description:

Anakinra 100 mg given daily by subcutaneous injection for 14 days

Treatment:

Drug: Anakinra

Placebo

Placebo Comparator group

Description:

0.67 ml of NaCl 0.9% solution

Treatment:

Drug: Placebo