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

NCT01491074 | Completed Phase 2 DMC

• 6 other identifiers: 2010/1971 [REK]2010-021953-372010/197110/15070-449472010/19043
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-ST Elevation Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

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

  0-56 hrs following inclusion

Secondary Outcomes (8)

• hs troponin T

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

• hs CRP

  3 and 6 months following inclusion

• pro-BNP

  0-56 hrs, 3 and 6 months

• Infarct size

  6 months

• LV size

  acute phase (0-3 days), 6 months

Other Outcomes (1)

• Other inflammatory pathways

  0-56 hrs, 3 monhts, 6 months

Study Arms (2)

NaCl 0.9% 100 ml

PLACEBO COMPARATOR

Drug: NaCl 0.9% 100 ml

Tocilizumab 280 mg

EXPERIMENTAL

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

Drug: Tocilizumab 280 mg

Interventions

Tocilizumab 280 mg DRUG

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

Also known as: Brand name RoActemra (Roche), ATC: L04A C07

Tocilizumab 280 mg

NaCl 0.9% 100 ml DRUG

Placebo

NaCl 0.9% 100 ml

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NSTEMI (ESC Type 1)
• Age 18-80 years
• Troponin T \>/= 30 ng/ml
• Informed consent to participation

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Oslo University Hospital

Oslo, Oslo County, 0424, Norway

Location

St Olavs Hospital

Trondheim, Sør-Trøndelag, 7006, Norway

Location

Related Publications (3)

• Aherrahrou R, Reinberger T, Hashmi S, Erdmann J. GWAS breakthroughs: mapping the journey from one locus to 393 significant coronary artery disease associations. Cardiovasc Res. 2024 Nov 5;120(13):1508-1530. doi: 10.1093/cvr/cvae161.

  PMID: 39073758 DERIVED

• 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.

  PMID: 30258647 DERIVED

• 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.

  PMID: 29961572 DERIVED

MeSH Terms

Conditions

Non-ST Elevated Myocardial Infarction

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Lars Gullestad, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• 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 CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2011
• First Posted: December 13, 2011
• Study Start: August 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: April 1, 2014
• Last Updated: May 19, 2014

Record last verified: 2014-05

Locations

NO (2)