Anakinra to Prevent Adverse Post-infarction Remodeling (2)
Condition: Acute Myocardial Infarction; Heart Failure
MeSH terms: Heart Failure; Myocardial Infarction; Infarction
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Anakinra; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Anakinra 100 mg s.c. daily for 14 days; 0.67 ml of NaCl 0.9% solution given subcutaneously daily for 14 days
Other intervention name(s): Kineret; NaCl 0.9%
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Acute myocardial infarction; Heart Failure; Cardiac Remodeling