NCT03004703

ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (actual)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Coronary Disease
• Myocardial Infarction

Interventions

Type	Name	Description
DRUG	Tocilizumab	Active drug: Tocilizumab, 20 mg/ml; 14 ml (280 mg) dissolved in 100 ml NaCl 0.9 % i.v. once.
DRUG	Sodium chloride 0.9%	Placebo: Sodium chloride 0.9%; 100 ml i.v. once.

Timeline

• Start date: 2017-03-16
• Primary completion: 2020-02-19
• Completion: 2021-02-10
• First posted: 2016-12-29
• Last updated: 2021-03-02

Locations

3 sites across 1 country: Norway