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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non-ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Tocilizumab 280 mg
* Drug: NaCl 0.9% 100 ml


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: NaCl 0.9% 100 ml<br> | Drug: NaCl 0.9% 100 ml<br>* Placebo<br>|
| Experimental: Tocilizumab 280 mg<br>Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl | Drug: Tocilizumab 280 mg<br>* Intravenous administration of 280 mg Tocilizumab (14 ml), mixed with 86 ml 0.9% NaCl<br>* Other names: ATC: L04A C07;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| high sensitivity C-reactive protein Area under the curve (AUC) |  | 0-56 hrs following inclusion | 

Secondary Outcome Measures

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