Anakinra to Prevent Post-infarction Remodeling
Condition: ST Segment Elevation Acute Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Intervention: Anakinra; Placebo
Intervention description: 100 mg daily subcutaneous injection for 14 days; 0.67 ml of NaCl 0.9% subcutaneously daily for 14 days
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: acute myocardial infarction

Summary:

      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.
    

Eligibility criteria:

        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