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

This study has been completed.
Sponsor:
Collaborators:
St. Olavs Hospital
South-Eastern Norway Regional Health Authority
University of Oslo
Norwegian University of Science and Technology
Information provided by (Responsible Party):
Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01491074
First received: December 9, 2011
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Non-ST Elevation Myocardial Infarction
Drug: Tocilizumab 280 mg
Drug: NaCl 0.9% 100 ml
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • high sensitivity C-reactive protein Area under the curve (AUC) [ Time Frame: 0-56 hrs following inclusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • hs troponin T [ Time Frame: 0-56 hrs, 3 months and 6 months following inclusion ] [ Designated as safety issue: No ]
  • hs CRP [ Time Frame: 3 and 6 months following inclusion ] [ Designated as safety issue: No ]
  • pro-BNP [ Time Frame: 0-56 hrs, 3 and 6 months ] [ Designated as safety issue: No ]
  • Infarct size [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed by Echocardiography and MRI at 6 months

  • LV size [ Time Frame: acute phase (0-3 days), 6 months ] [ Designated as safety issue: No ]
    Assessed by echocardiography

  • LV function [ Time Frame: acute phase (0-3 days), 6 months ] [ Designated as safety issue: No ]
    Assessed by echocardiography, cardiac MRI at 6 months

  • Coronary flow reserve [ Time Frame: acute phase (0-3 days), 6 months ] [ Designated as safety issue: No ]
    Assesses coronary microvascular function - for 60 patients only.

  • Endothelial function [ Time Frame: Acute phase (0-3 days) and 6 months ] [ Designated as safety issue: No ]
    Assessed by tonometry


Other Outcome Measures:
  • Other inflammatory pathways [ Time Frame: 0-56 hrs, 3 monhts, 6 months ] [ Designated as safety issue: No ]
    TNF-alfa, IL-1, IL-6, IL-18, platelet-derived inflammatory mediators, anti-inflammatory cytokines etc


Enrollment: 120
Study Start Date: August 2011
Study Completion Date: April 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491074

Locations
Norway
St Olavs Hospital
Trondheim, Sør-Trøndelag, Norway, 7006
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
  More Information

No publications provided

Responsible Party: Oslo University Hospital
ClinicalTrials.gov Identifier: NCT01491074     History of Changes
Other Study ID Numbers: 2010/1971 [REK], 2010-021953-37, 2010/1971, 10/15070-4, 4947, 2010/19043
Study First Received: December 9, 2011
Last Updated: May 16, 2014
Health Authority: Norway: The National Committees for Research Ethics in Norway (REK)
Norway: Norwegian Medicines Agency (SLV)
Norway: Norwegian Social Science Data Services (NSD)

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014