ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial
Condition: Coronary Disease; Myocardial Infarction
MeSH terms: Myocardial Infarction; Coronary Disease; Infarction
Study type: Interventional
Phase: Phase 2

Summary: 
      The main goal of this study is to evaluate the ability of a single administration of
      tocilizumab to reduce myocardial damage in patients presenting with an acute ST-segment
      elevation myocardial infarction (STEMI). Secondary objectives are to assess the impact of
      treatment on: (i) final infarct size, (ii) left ventricular size and function, (iii)
      inflammation, (iv) extracellular matrix remodeling, (v) lipid parameters, (vi) platelet
      activation and additional pro- and anti-thrombotic parameters, and (vii) study drug safety
      and tolerability.
    

Detailed description: 
      Myocardial infarction (MI) is a major contributor to morbidity and mortality in the Western
      world. The main determinant of death and complications is infarct size, and limitation of the
      infarct size has therefore been an important objective for strategies to improve outcome. In
      patients presenting with an acute ST segment elevation myocardial infarction (STEMI), urgent
      myocardial reperfusion with percutaneous coronary intervention (PCI) is the most effective
      treatment to this end. However, despite PCI, the morbidity and mortality in patients with
      STEMI remain substantial. This fact suggests that other, adjuvant strategies are required to
      reduce infarct size and improve outcome. The inflammatory cytokine interleukin (IL)-6 is an
      important mediator of plaque destabilisation and rupture in acute coronary syndrome (ACS) and
      may contribute to the ischemia-reperfusion injury succeeding revascularisation. Experimental
      studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory
      mechanisms.(ref)

      The investigators recently conducted a double blind, placebo controlled trial in 117 patients
      with non-ST segment elevation myocardial infarction (NSTEMI) who presented within 72 hour
      after the onset of chest pain. In this study, a single, intravenous dose of the IL-6
      antagonist tocilizumab reduced the inflammatory activity by more than 50% in the days
      subsequent to the intervention. Importantly, tocilizumab also reduced troponin T (TnT)
      levels, suggesting that patients receiving tocilizumab sustained less myocardial damage than
      patients who received placebo.1

      Interleukin-6 inhibition might limit infarct size through reduced myocardial inflammation,
      but theoretically, it could also inhibit the repair process within the injured area. While
      the recent study suggests that IL-6 inhibition has largely favourable effects in NSTEMI, it
      remains to be seen if similar, beneficial effects can be obtained in patients with STEMI. On
      this background, the investigators want to investigate the effect of tocilizumab in patients
      with acute STEMI. The postulate is that a single dose of tocilizumab (RoActemra®) will have
      favourable effects on infarct size, as assessed by markers of myocardial necrosis and cardiac
      magnetic resonance imaging (CMR), without negative consequences for the repair process in
      these patients. The hypothesis will be tested in a randomised, double blind, placebo
      controlled trial comprising 200 patients with acute STEMI.

      This is a phase 2 study on a new and exciting anti-inflammatory strategy in cardiovascular
      disease. It will be conducted at three experienced, high volume centres in Norway, and will
      target new and yet unmodified mechanisms during myocardial infarction. The ambition is to
      improve the prognosis of patients with ACS, with potential to change clinical practice.
    

Intervention name(s): Tocilizumab; Sodium chloride 0.9%
Intervention type(s): Drug; Drug
Intervention description(s): Active drug: Tocilizumab, 20 mg/ml; 14 ml (280 mg) dissolved in 100 ml NaCl 0.9 % i.v. once.; Placebo: Sodium chloride 0.9%; 100 ml i.v. once.
Other intervention name(s): RoActemra®,; NaCl 0.9%
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Interleukin 6; Tocilizumab; Acute coronary syndrome; STEMI; Inflammation