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

Primary Purpose

Non-ST Elevation Myocardial Infarction

Status

Completed

Phase

Phase 2

Locations

Norway

Study Type

Interventional

Intervention

Tocilizumab 280 mg

NaCl 0.9% 100 ml

About this trial

This is an interventional treatment trial for Non-ST Elevation Myocardial Infarction

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

St Olavs Hospital
Oslo University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

NaCl 0.9% 100 ml

Tocilizumab 280 mg

Arm Description

Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl

Outcomes

Primary Outcome Measures

high sensitivity C-reactive protein Area under the curve (AUC)

Secondary Outcome Measures

hs troponin T

hs CRP

pro-BNP

Infarct size

Assessed by Echocardiography and MRI at 6 months

LV size

Assessed by echocardiography

LV function

Assessed by echocardiography, cardiac MRI at 6 months

Coronary flow reserve

Assesses coronary microvascular function - for 60 patients only.

Endothelial function

Assessed by tonometry

Full Information

NCT ID

NCT01491074

First Posted

December 9, 2011

Last Updated

May 16, 2014

Sponsor

Oslo University Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01491074

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Oslo University Hospital

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-ST Elevation Myocardial Infarction

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NaCl 0.9% 100 ml

Arm Type

Placebo Comparator

Arm Title

Tocilizumab 280 mg

Arm Type

Experimental

Arm Description

Intravenous infusion, 280 mg Tocilizumab (14 ml) added to 86 ml of 0.9% NaCl

Intervention Type

Drug

Intervention Name(s)

Tocilizumab 280 mg

Other Intervention Name(s)

Brand name RoActemra (Roche), ATC: L04A C07

Intervention Description

Intravenous administration of 280 mg Tocilizumab (14 ml), mixed with 86 ml 0.9% NaCl

Intervention Type

Drug

Intervention Name(s)

NaCl 0.9% 100 ml

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

high sensitivity C-reactive protein Area under the curve (AUC)

Time Frame

0-56 hrs following inclusion

Secondary Outcome Measure Information:

Title

hs troponin T

Time Frame

0-56 hrs, 3 months and 6 months following inclusion

Title

hs CRP

Time Frame

3 and 6 months following inclusion

Title

pro-BNP

Time Frame

0-56 hrs, 3 and 6 months

Title

Infarct size

Description

Assessed by Echocardiography and MRI at 6 months

Time Frame

6 months

Title

LV size

Description

Assessed by echocardiography

Time Frame

acute phase (0-3 days), 6 months

Title

LV function

Description

Assessed by echocardiography, cardiac MRI at 6 months

Time Frame

acute phase (0-3 days), 6 months

Title

Coronary flow reserve

Description

Assesses coronary microvascular function - for 60 patients only.

Time Frame

acute phase (0-3 days), 6 months

Title

Endothelial function

Description

Assessed by tonometry

Time Frame

Acute phase (0-3 days) and 6 months

Other Pre-specified Outcome Measures:

Title

Other inflammatory pathways

Description

TNF-alfa, IL-1, IL-6, IL-18, platelet-derived inflammatory mediators, anti-inflammatory cytokines etc

Time Frame

0-56 hrs, 3 monhts, 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lars Gullestad, MD, PhD

Organizational Affiliation

Oslo University Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Rune Wiseth, MD, PhD

Organizational Affiliation

St. Olavs Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Pål Aukrust, MD, PhD

Organizational Affiliation

Oslo University Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jan K Damås, MD, PhD

Organizational Affiliation

St. Olavs Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

St Olavs Hospital

City

Trondheim

State/Province

Sør-Trøndelag

ZIP/Postal Code

7006

Country

Norway

Facility Name

Oslo University Hospital

City

Oslo

ZIP/Postal Code

0424

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

30258647

Citation

Ueland T, Kleveland O, Michelsen AE, Wiseth R, Damas JK, Aukrust P, Gullestad L, Halvorsen B, Yndestad A. Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction. Open Heart. 2018 Sep 18;5(2):e000765. doi: 10.1136/openhrt-2017-000765. eCollection 2018.

Results Reference

derived

PubMed Identifier

29961572

Citation

Kleveland O, Ueland T, Kunszt G, Bratlie M, Yndestad A, Broch K, Holte E, Ryan L, Amundsen BH, Bendz B, Aakhus S, Espevik T, Halvorsen B, Mollnes TE, Wiseth R, Gullestad L, Aukrust P, Damas JK. Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1beta in non-ST-elevation myocardial infarction. Int J Cardiol. 2018 Nov 15;271:1-7. doi: 10.1016/j.ijcard.2018.04.136. Epub 2018 Jun 29.

Results Reference

derived

Learn more about this trial

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

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