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

• Sponsor: Oslo University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01491074
• Collaborator: St. Olavs Hospital (Other), South-Eastern Norway Regional Health Authority (Other), University of Oslo (Other), Norwegian University of Science and Technology (Other)
• Enrollment: 120
• Locations: 2
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 60
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-ST Elevation Myocardial Infarction	Drug: Tocilizumab 280 mg; Drug: NaCl 0.9% 100 ml	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• 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.
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: NaCl 0.9% 100 ml	Drug: NaCl 0.9% 100 ml; Placebo
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; Other Names: Brand name RoActemra (Roche) ATC: L04A C07

Outcome Measures

Primary Outcome Measures

1. high sensitivity C-reactive protein Area under the curve (AUC) [0-56 hrs following inclusion]

Secondary Outcome Measures

1. hs troponin T [0-56 hrs, 3 months and 6 months following inclusion]

2. hs CRP [3 and 6 months following inclusion]

3. pro-BNP [0-56 hrs, 3 and 6 months]

4. Infarct size [6 months]

   Assessed by Echocardiography and MRI at 6 months

5. LV size [acute phase (0-3 days), 6 months]

   Assessed by echocardiography

6. LV function [acute phase (0-3 days), 6 months]

   Assessed by echocardiography, cardiac MRI at 6 months

7. Coronary flow reserve [acute phase (0-3 days), 6 months]

   Assesses coronary microvascular function - for 60 patients only.

8. Endothelial function [Acute phase (0-3 days) and 6 months]

   Assessed by tonometry

Other Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St Olavs Hospital	Trondheim	Sør-Trøndelag	Norway	7006
2	Oslo University Hospital	Oslo		Norway	0424

Sponsors and Collaborators

• Oslo University Hospital
• St. Olavs Hospital
• South-Eastern Norway Regional Health Authority
• University of Oslo
• Norwegian University of Science and Technology

Investigators

• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Oslo University Hospital
• ClinicalTrials.gov Identifier: NCT01491074
• Other Study ID Numbers: 2010/1971 [REK]; 2010-021953-37; 2010/1971; 10/15070-4; 4947; 2010/19043
• First Posted: Dec 13, 2011
• Last Update Posted: May 19, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Infarction

Study Results

No Results Posted as of May 19, 2014