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

Non-ST Elevation Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01491074
• Other study ID #: 2010/1971 [REK]
• Secondary ID: 2010-021953-3720
• Status: Completed
• Phase: Phase 2
• First received: December 9, 2011
• Last updated: May 16, 2014
• Start date: August 2011
• Est. completion date: April 2014

Study information

• Verified date: May 2014
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: The National Committees for Research Ethics in Norway (REK)Norway: Norwegian Medicines Agency (SLV)Norway: Norwegian Social Science Data Services (NSD)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: April 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Non-ST Elevation Myocardial Infarction

Intervention

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

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo
Norway	St Olavs Hospital	Trondheim	Sør-Trøndelag

Sponsors (5)

Lead Sponsor	Collaborator
Oslo University Hospital	Norwegian University of Science and Technology, South-Eastern Norway Regional Health Authority, St. Olavs Hospital, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other inflammatory pathways	TNF-alfa, IL-1, IL-6, IL-18, platelet-derived inflammatory mediators, anti-inflammatory cytokines etc	0-56 hrs, 3 monhts, 6 months	No
Primary	high sensitivity C-reactive protein Area under the curve (AUC)		0-56 hrs following inclusion	No
Secondary	hs troponin T		0-56 hrs, 3 months and 6 months following inclusion	No
Secondary	hs CRP		3 and 6 months following inclusion	No
Secondary	pro-BNP		0-56 hrs, 3 and 6 months	No
Secondary	Infarct size	Assessed by Echocardiography and MRI at 6 months	6 months	No
Secondary	LV size	Assessed by echocardiography	acute phase (0-3 days), 6 months	No
Secondary	LV function	Assessed by echocardiography, cardiac MRI at 6 months	acute phase (0-3 days), 6 months	No
Secondary	Coronary flow reserve	Assesses coronary microvascular function - for 60 patients only.	acute phase (0-3 days), 6 months	No
Secondary	Endothelial function	Assessed by tonometry	Acute phase (0-3 days) and 6 months	No