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

Phase 2

Completed

• Conditions: Non-ST Elevation Myocardial Infarction
• Interventions: Drug: Tocilizumab 280 mg; Drug: NaCl 0.9% 100 ml

• Registration Number: NCT01491074
• Lead Sponsor: Oslo University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-12-09
• Study First Submitted QC: 2011-12-12
• Study First Posted: 2011-12-13
• Primary Completion: 2013-11
• Study Completion: 2014-04
• Status Verified: 2014-05
• Last Update Submitted: 2014-05-16
• Last Update Posted: 2014-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab 280 mg	Tocilizumab 280 mg	Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl
NaCl 0.9% 100 ml	NaCl 0.9% 100 ml	-

Primary Outcome Measures

Name	Time	Method
high sensitivity C-reactive protein Area under the curve (AUC)	0-56 hrs following inclusion

Secondary Outcome Measures

Name	Time	Method
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	6 months	Assessed by Echocardiography and MRI at 6 months
LV size	acute phase (0-3 days), 6 months	Assessed by echocardiography
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

Trial Locations

Locations (2)

St Olavs Hospital; 🇳🇴 Trondheim, Sør-Trøndelag, Norway

Oslo University Hospital; 🇳🇴 Oslo, Norway