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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)
  1. Anne Kristine Anstensrud1,2,
  2. Sindre Woxholt3,4,
  3. Kapil Sharma5,
  4. Kaspar Broch1,6,
  5. Bjørn Bendz1,2,
  6. Svend Aakhus4,
  7. Thor Ueland7,8,
  8. Brage H Amundsen3,4,
  9. Jan Kristian Damås9,10,
  10. Einar Hopp11,
  11. Ola Kleveland3,4,
  12. Knut Haakon Stensæth4,12,
  13. Anders Opdahl1,
  14. Nils-Einar Kløw2,13,
  15. Ingebjørg Seljeflot2,14,
  16. Geir Øystein Andersen5,14,
  17. Rune Wiseth3,4,
  18. Pål Aukrust2,15 and
  19. Lars Gullestad1,2
  1. 1Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  2. 2Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  3. 3Clinic of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  4. 4Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  5. 5Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
  6. 6K.G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway
  7. 7Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  8. 8K.G.Jebsen Thrombosis Research and Expertise Center (TREC), The Arctic University of Norway, Tromsø, Norway
  9. 9Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Oslo, Norway
  10. 10Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
  11. 11Division of Radiology and Nuclear Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  12. 12Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  13. 13Department of Radiology, Oslo University Hospital Ullevaal, Oslo, Norway
  14. 14Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway
  15. 15Department of Rheumatology, Dermatology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway
  1. Correspondence to Anne Kristine Anstensrud; annans{at}ous-hf.no

Abstract

Introduction Interleukin-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 analysis The 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 dissemination Based 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.

Registration Clinicaltrials.gov, identifier NCT03004703.

  • coronary artery disease
  • Myocardial Ischaemia and Infarction (IHD)
  • inflammation
  • cytokines
  • MRI

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Footnotes

  • Funding The ASSAIL-MI trial is an investigator-initiated study supported by unrestricted grants provided by the South-Eastern Norway Regional Health Authority. F.Hoffmann-La Roche Ltd, Grenacherstrasse 124, 4070 Basel, Switzerland has provided the investigational medicinal product used in this trial and has also provided an unrestricted sum for the implementation of the study. The funding sources have no role in the design of the study; neither will they participate in the implementation of the trial, in the analyses of the results, or in the decision to publish. The investigators take sole responsibility for the integrity of the data, the writing of the manuscript and the dissemination of the results.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Regional Committee for Medical and Health Research Ethics of South-Eastern Norway and the Norwegian Medicines Agency.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data availability statement Data are available in a public, open access repository.

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