Clinical trial NCT01491074: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-ST Elevation Myocardial Infarction
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
name: South-Eastern Norway Regional Health Authority
name: University of Oslo
name: Norwegian University of Science and Technology
First posted: 2011-12-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: high sensitivity C-reactive protein Area under the curve (AUC)
timeFrame: 0-56 hrs following inclusion
Secondary outcomes:
measure: hs troponin T
timeFrame: 0-56 hrs, 3 months and 6 months following inclusion
measure: hs CRP
timeFrame: 3 and 6 months following inclusion
measure: pro-BNP
timeFrame: 0-56 hrs, 3 and 6 months
measure: Infarct size
timeFrame: 6 months
measure: LV size
timeFrame: acute phase (0-3 days), 6 months
measure: LV function
timeFrame: acute phase (0-3 days), 6 months
measure: Coronary flow reserve
timeFrame: acute phase (0-3 days), 6 months
measure: Endothelial function
timeFrame: Acute phase (0-3 days) and 6 months
Other outcomes:
measure: Other inflammatory pathways
timeFrame: 0-56 hrs, 3 monhts, 6 months
Locations:
city: Trondheim
country: Norway
facility: St Olavs Hospital
state: Sør-Trøndelag
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Lars Gullestad, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Olavs Hospital
name: Rune Wiseth, MD, PhD
role: STUDY_CHAIR
affiliation: Oslo University Hospital
name: Pål Aukrust, MD, PhD
role: STUDY_CHAIR
affiliation: St. Olavs Hospital
name: Jan K Damås, MD, PhD
role: STUDY_CHAIR
References:
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.
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.