Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI)

Abstract

IntroductionInterleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the ASSessing the effect of Anti-IL-6 treatment in MI (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).Methods and analysisThe ASSAIL-MI trial is a randomised, double blind, placebo-controlled trial, conducted at three high-volume percutaneous coronary intervention (PCI) centres in Norway. 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain will be randomised to receive tocilizumab or matching placebo prior to PCI. The patients are followed-up for 6 months. The primary endpoint is the myocardial salvage index measured by cardiac MRI (CMR) 3–7 days after the intervention. Secondary endpoints include final infarct size measured by CMR and plasma markers of myocardial necrosis. Efficacy and safety assessments during follow-up include blood sampling, echocardiography and CMR.Ethics and disseminationBased on previous experience the study is considered feasible and safe. If tocilizumab increases myocardial salvage, further endpoint-driven multicentre trials may be initiated. The ASSAIL-MI trial has the potential to change clinical practice in patients with STEMI.RegistrationClinicaltrials.gov, identifier NCT03004703.

Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

“…The results showed a negligible effect on the level of IL-1 β and IL-6 and the number of MACE [ 68 ]. Similarly, ACS patients administered with the IL-6 inhibitor tocilizumab showed a reduced level of troponin and inflammatory markers in the ASSessing the Effect of Anti-IL-6 Treatment in MI (ASSAIL-MI) trial [ 16 , 69 , 70 ], which was designed to assess the effects of tocilizumab on ischemia reperfusion injury in patients with ST-elevation myocardial infarction. The neutral results in the CIRT trial suggest that future targeted inflammatory therapies should focus on the control of specific inflammatory cytokines or immune cells [ 16 ].…”

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction

“…However, our results indicate that, among hundreds of circulating proteins not routinely assayed in clinical setting of MI, IL-6 and ST2 appear to potentially carry valuable prognostic information. Ongoing randomized trials of tocilizumab, a monoclonal antibody targeting IL-6 receptors may add further insight 39 .…”

Cytokines as therapeutic targets for cardio- and cerebrovascular diseases

“…Overall, since none of the trials reported significant adverse events associated with the treatment, investigation on this topic is still ongoing. In particular, the “ASSessing the effect of Anti-IL-6 treatment in MI” (ASSAIL-MI) trial [ 12 ] was recently completed, and its results are awaited. Compared to previous trials, the ASSAIL-MI enrolled patients with STEMI and aimed at investigating, as a primary endpoint, the effects of tocilizumab on myocardial salvage, evaluated through cardiac magnetic resonance imaging.…”