Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Non-ST Elevation Myocardial Infarction

Overview

Acute coronary syndromes (ACS) are still associated with high morbidity and mortality, despite several improvements in their management. This may indicate that important pathogenic mechanisms contribute to both stable and unstable atherosclerotic disease mechanisms. Based upon previous research, the investigators believe that providing a block in the damaging inflammatory loop though short term inhibition of Interleukin-6 receptor signalling, could be an attractive therapeutic target in ACS; and of particular interest in patients with non-ST elevation myocardial infarction (NSTEMI), a disease often characterized by widespread coronary inflammation with multiple unstable plaques. The investigators hypothesize that a single administration of the anti-Interleukin 6 receptor antagonist Tocilizumab, in patients with NSTEMI, may interrupt the self-perpetuating inflammatory loops which could improve plaque stability, with potential secondary beneficial effects on myocardial damage. This will be investigated in a randomized, double blind, placebo-controlled study, including a total of 120 patients.

Full Title of Study: “Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Non-ST Elevation Myocardial Infarction – a Randomized, Double Blind, Placebo Controlled Study.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2013

Interventions

  • Drug: Tocilizumab 280 mg
    • Intravenous administration of 280 mg Tocilizumab (14 ml), mixed with 86 ml 0.9% NaCl
  • Drug: NaCl 0.9% 100 ml
    • Placebo

Arms, Groups and Cohorts

  • Placebo Comparator: NaCl 0.9% 100 ml
  • Experimental: Tocilizumab 280 mg
    • Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl

Clinical Trial Outcome Measures

Primary Measures

  • high sensitivity C-reactive protein Area under the curve (AUC)
    • Time Frame: 0-56 hrs following inclusion

Secondary Measures

  • hs troponin T
    • Time Frame: 0-56 hrs, 3 months and 6 months following inclusion
  • hs CRP
    • Time Frame: 3 and 6 months following inclusion
  • pro-BNP
    • Time Frame: 0-56 hrs, 3 and 6 months
  • Infarct size
    • Time Frame: 6 months
    • Assessed by Echocardiography and MRI at 6 months
  • LV size
    • Time Frame: acute phase (0-3 days), 6 months
    • Assessed by echocardiography
  • LV function
    • Time Frame: acute phase (0-3 days), 6 months
    • Assessed by echocardiography, cardiac MRI at 6 months
  • Coronary flow reserve
    • Time Frame: acute phase (0-3 days), 6 months
    • Assesses coronary microvascular function – for 60 patients only.
  • Endothelial function
    • Time Frame: Acute phase (0-3 days) and 6 months
    • Assessed by tonometry

Participating in This Clinical Trial

Inclusion Criteria

  • NSTEMI (ESC Type 1) – Age 18-80 years – Troponin T >/= 30 ng/ml – Informed consent to participation Exclusion Criteria:

  • STEMI – Known cardiac disease, except coronary disease (cardiomyopathy, heart failure with known EF < 45%, severe valvular heart disease attending regular follow-up, recent PCI/ACB (< 3 months)) – Hemodynamic and/or respiratory instability – Cardiac arrest in acute phase – Concurrent condition affecting/potentially affecting CRP (infection, malignancy, autoimmune disease) – Recent major surgery (< 3 months) – Recent/concurrent immunosuppressant treatment (< 2 weeks, except NSAIDs) – Severe renal failure (eGFR < 30 ml/min) – Pregnancy – Contraindications to any study investigations and/or medication. – Expected non-adherence to study protocol

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Oslo University Hospital
  • Collaborator
    • St. Olavs Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Lars Gullestad, MD, PhD, Principal Investigator, Oslo University Hospital
    • Rune Wiseth, MD, PhD, Study Chair, St. Olavs Hospital
    • Pål Aukrust, MD, PhD, Study Chair, Oslo University Hospital
    • Jan K Damås, MD, PhD, Study Chair, St. Olavs Hospital

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