Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Non-ST Elevation Myocardial Infarction
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.
|Non-ST Elevation Myocardial Infarction||Drug: Tocilizumab 280 mg Drug: NaCl 0.9% 100 ml||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Non-ST Elevation Myocardial Infarction - a Randomized, Double Blind, Placebo Controlled Study.|
- high sensitivity C-reactive protein Area under the curve (AUC) [ Time Frame: 0-56 hrs following inclusion ]
- 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
- Other inflammatory pathways [ Time Frame: 0-56 hrs, 3 monhts, 6 months ]TNF-alfa, IL-1, IL-6, IL-18, platelet-derived inflammatory mediators, anti-inflammatory cytokines etc
|Study Start Date:||August 2011|
|Study Completion Date:||April 2014|
|Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
|Placebo Comparator: NaCl 0.9% 100 ml||
Drug: NaCl 0.9% 100 ml
Experimental: Tocilizumab 280 mg
Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl
Drug: Tocilizumab 280 mg
Intravenous administration of 280 mg Tocilizumab (14 ml), mixed with 86 ml 0.9% NaCl
Please refer to this study by its ClinicalTrials.gov identifier: NCT01491074
|St Olavs Hospital|
|Trondheim, Sør-Trøndelag, Norway, 7006|
|Oslo University Hospital|
|Oslo, Norway, 0424|
|Principal Investigator:||Lars Gullestad, MD, PhD||Oslo University Hospital|
|Study Chair:||Rune Wiseth, MD, PhD||St. Olavs Hospital|
|Study Chair:||Pål Aukrust, MD, PhD||Oslo University Hospital|
|Study Chair:||Jan K Damås, MD, PhD||St. Olavs Hospital|