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

NCT ID: NCT01491074

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-04-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NaCl 0.9% 100 ml

Group Type: PLACEBO_COMPARATOR

NaCl 0.9% 100 ml

Intervention Type: DRUG

Placebo

Tocilizumab 280 mg

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

Group Type: EXPERIMENTAL

Tocilizumab 280 mg

Intervention Type: DRUG

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

Interventions

Tocilizumab 280 mg

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

Intervention Type: DRUG

NaCl 0.9% 100 ml

Placebo

Intervention Type: DRUG

Other Intervention Names

Brand name RoActemra (Roche); ATC: L04A C07

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

South-Eastern Norway Regional Health Authority

OTHER

Sponsor Role: collaborator

University of Oslo

OTHER

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars Gullestad, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Rune Wiseth, MD, PhD

Role: STUDY_CHAIR

St. Olavs Hospital

Pål Aukrust, MD, PhD

Role: STUDY_CHAIR

Oslo University Hospital

Jan K Damås, MD, PhD

Role: STUDY_CHAIR

St. Olavs Hospital

Locations

Oslo University Hospital

Oslo, Oslo County, Norway

St Olavs Hospital

Trondheim, Sør-Trøndelag, Norway

Countries

Norway

References

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.

Reference Type: DERIVED

PMID: 39073758 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30258647 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29961572 (View on PubMed)

Other Identifiers

2010-021953-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2010/1971

Identifier Type: REGISTRY

Identifier Source: secondary_id

10/15070-4

Identifier Type: REGISTRY

Identifier Source: secondary_id

4947

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2010/19043

Identifier Type: OTHER

Identifier Source: secondary_id

2010/1971 [REK]

Identifier Type: -

Identifier Source: org_study_id