Non-ST Elevation Myocardial Infarction
Conditions
Brief summary
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.
Interventions
DRUGTocilizumab 280 mg
Intravenous administration of 280 mg Tocilizumab (14 ml), mixed with 86 ml 0.9% NaCl
DRUGNaCl 0.9% 100 ml
Placebo
Sponsors
St. Olavs Hospital
South-Eastern Norway Regional Health Authority
University of Oslo
Norwegian University of Science and Technology
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| high sensitivity C-reactive protein Area under the curve (AUC) | 0-56 hrs following inclusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infarct size | 6 months | Assessed by Echocardiography and MRI at 6 months |
| LV size | acute phase (0-3 days), 6 months | Assessed by echocardiography |
| hs troponin T | 0-56 hrs, 3 months and 6 months following inclusion | — |
| hs CRP | 3 and 6 months following inclusion | — |
| LV function | acute phase (0-3 days), 6 months | Assessed by echocardiography, cardiac MRI at 6 months |
| Coronary flow reserve | acute phase (0-3 days), 6 months | Assesses coronary microvascular function - for 60 patients only. |
| Endothelial function | Acute phase (0-3 days) and 6 months | Assessed by tonometry |
| pro-BNP | 0-56 hrs, 3 and 6 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Other inflammatory pathways | 0-56 hrs, 3 monhts, 6 months | TNF-alfa, IL-1, IL-6, IL-18, platelet-derived inflammatory mediators, anti-inflammatory cytokines etc |
Countries
Norway
Outcome results
None listed