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Trial record 1 of 1 for:    NCT03004703
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ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial (ASSAIL-MI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03004703
Recruitment Status : Active, not recruiting
First Posted : December 29, 2016
Last Update Posted : March 4, 2020
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):
Lars Gullestad, Oslo University Hospital

Brief Summary:
The main goal of this study is to evaluate the ability of a single administration of tocilizumab to reduce myocardial damage in patients presenting with an acute ST-segment elevation myocardial infarction (STEMI). Secondary objectives are to assess the impact of treatment on: (i) final infarct size, (ii) left ventricular size and function, (iii) inflammation, (iv) extracellular matrix remodeling, (v) lipid parameters, (vi) platelet activation and additional pro- and anti-thrombotic parameters, and (vii) study drug safety and tolerability.

Condition or disease Intervention/treatment Phase
Coronary Disease Myocardial Infarction Drug: Tocilizumab Drug: Sodium chloride 0.9% Phase 2

Detailed Description:

Myocardial infarction (MI) is a major contributor to morbidity and mortality in the Western world. The main determinant of death and complications is infarct size, and limitation of the infarct size has therefore been an important objective for strategies to improve outcome. In patients presenting with an acute ST segment elevation myocardial infarction (STEMI), urgent myocardial reperfusion with percutaneous coronary intervention (PCI) is the most effective treatment to this end. However, despite PCI, the morbidity and mortality in patients with STEMI remain substantial. This fact suggests that other, adjuvant strategies are required to reduce infarct size and improve outcome. The inflammatory cytokine interleukin (IL)-6 is an important mediator of plaque destabilisation and rupture in acute coronary syndrome (ACS) and may contribute to the ischemia-reperfusion injury succeeding revascularisation. Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms.(ref)

The investigators recently conducted a double blind, placebo controlled trial in 117 patients with non-ST segment elevation myocardial infarction (NSTEMI) who presented within 72 hour after the onset of chest pain. In this study, a single, intravenous dose of the IL-6 antagonist tocilizumab reduced the inflammatory activity by more than 50% in the days subsequent to the intervention. Importantly, tocilizumab also reduced troponin T (TnT) levels, suggesting that patients receiving tocilizumab sustained less myocardial damage than patients who received placebo.1

Interleukin-6 inhibition might limit infarct size through reduced myocardial inflammation, but theoretically, it could also inhibit the repair process within the injured area. While the recent study suggests that IL-6 inhibition has largely favourable effects in NSTEMI, it remains to be seen if similar, beneficial effects can be obtained in patients with STEMI. On this background, the investigators want to investigate the effect of tocilizumab in patients with acute STEMI. The postulate is that a single dose of tocilizumab (RoActemra®) will have favourable effects on infarct size, as assessed by markers of myocardial necrosis and cardiac magnetic resonance imaging (CMR), without negative consequences for the repair process in these patients. The hypothesis will be tested in a randomised, double blind, placebo controlled trial comprising 200 patients with acute STEMI.

This is a phase 2 study on a new and exciting anti-inflammatory strategy in cardiovascular disease. It will be conducted at three experienced, high volume centres in Norway, and will target new and yet unmodified mechanisms during myocardial infarction. The ambition is to improve the prognosis of patients with ACS, with potential to change clinical practice.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial
Actual Study Start Date : March 16, 2017
Actual Primary Completion Date : February 19, 2020
Estimated Study Completion Date : July 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: Active drug
Tocilizumab, 20 mg/ml; 14 ml (280 mg) dissolved in 100 ml NaCl 0.9 % i.v. once.
Drug: Tocilizumab
Active drug: Tocilizumab, 20 mg/ml; 14 ml (280 mg) dissolved in 100 ml NaCl 0.9 % i.v. once.
Other Name: RoActemra®,

Placebo Comparator: Placebo
Sodium chloride 0.9%; 100 ml i.v. once.
Drug: Sodium chloride 0.9%
Placebo: Sodium chloride 0.9%; 100 ml i.v. once.
Other Name: NaCl 0.9%




Primary Outcome Measures :
  1. The primary endpoint will be the between-group difference in the myocardial salvage index as measured in the acute phase by cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE). [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. The between-group difference in the AUC for Troponin T (TnT) during index hospitalisation [ Time Frame: 24 -72 hours after randomisation ]
  2. The extent of microvascular obstruction as measured by CMR after 3 - 7 days [ Time Frame: 3 - 7 days after randomisation ]
  3. Final infarct size as measured by CMR 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  4. Left ventricular size as assessed by CMR 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  5. Baseline-adjusted NT-proBNP at 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  6. The AUC of Creatine Kinase-MB (CK-MB) during index hospitalisation [ Time Frame: 24-72 hours after randomisation ]
  7. The AUC of C-reactive protein (CRP) during index hospitalisation [ Time Frame: 24-72 hours after randomisation ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients will be screened for eligibility upon admittance due to acute STEMI at either participating site. All of the following conditions must apply to the prospective patient at screening prior to receiving study agent:

  • New ST elevation at the J-point in two contiguous leads (cut-points: 0.2mV in men and >0.15 mV in women in leads V2-V3 and/or >0.1 mV in other leads) in combination with symptoms consistent with acute MI.
  • Presentation within 6 hours of chest pain.
  • Indication for urgent coronary angiography with intent to reperfuse presumed occluded vessel.
  • Age between 18 and 80 years.
  • Informed consent obtained and documented according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

Patients will be excluded from the study if they meet any of the following criteria:

  • NSTEMI (non-ST segment elevation in ECG).
  • Left bundle branch block in ECG
  • History of previous MI
  • Cardiogenic shock.
  • Fibrinolytic therapy within 72 hours prior to admission.
  • Cardiac arrest / ventricular fibrillation.
  • History of severe renal failure with estimated glomerular filtration rate < 30 ml/minutes.
  • Known, current liver disease
  • History of concurrent inflammatory, biliary obstructive or malignant disease
  • A history of chronic or concurrent infectious disease, including a history of HIV, tuberculosis, or hepatitis B or C.
  • Known, uncontrolled lower gastrointestinal (GI) disease such as diverticulitis, Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that could predispose to GI perforations
  • Major surgery within 8 weeks prior or after baseline
  • History of central nervous system demyelinating or seizure disorders
  • History of primary or secondary immunodeficiency
  • Treatment with immunosuppressants other than low dose corticosteroids (equivalent to 5 mg of prednisone or less) at the time of randomisation
  • Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or to tocilizumab
  • Other contraindications to study medication
  • Pregnancy, possible pregnancy or breast-feeding - women of child-bearing potential or breastfeeding mothers cannot participate. A woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
  • Contraindications to CMR (pacemaker, CRT, ICD, certain ferromagnetic implants, severe claustrophobia, allergy to contrast medium).
  • Any condition/circumstances believed to interfere with the ability to comply with protocol.
  • Any reason why, in the opinion of the investigator, the patient should not participate.
  • Failure to obtain written, informed consent by patient or next of kin, for instance in case of patient death after consent has been provided in oral.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03004703


Locations
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Norway
Oslo University Hospital, Rikshospitalet
Oslo, Norway, 0424
Oslo University Hospital, Ullevål
Oslo, Norway, 0424
St. Olav Hospital
Trondheim, Norway, 7006
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
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Principal Investigator: Lars Gullestad, Professor, MD, PhD Oslo University Hospital
Study Chair: Bjørn Bendz, Associate Professor, MD, PhD Oslo University Hospital
Study Chair: Pål Aukrust, Professor, MD, PhD Oslo University Hospital
Study Chair: Svend Aakhus, Professor, MD, PhD Oslo University Hospital
Study Chair: Rune Wiseth, Professor, MD, PhD St. Olavs Hospital
Study Chair: Jan Kristian Damaas, Professor, MD, PhD St. Olavs Hospital
Study Chair: Geir Øystein Andersen, MD, PhD Oslo University Hospital, Ullevål
Study Chair: Nils Einar Kløw, Professor, MD, PhD Oslo University Hospital, Ullevål
Study Chair: Anders Opdahl, MD, PhD Oslo University Hospital, Ullevål
Publications:
Ibanez B, Macaya C, Sánchez-Brunete V, Pizarro G, Fernández-Friera L, Mateos A, Fernández-Ortiz A, García-Ruiz JM, García-Álvarez A, Iñiguez A, Jiménez-Borreguero J, López-Romero P, Fernández-Jiménez R, Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, Iglesias-Vázquez JA, Rodriguez MD, Escalera N, Acebal C, Cabrera JA, Valenciano J, Pérez de Prado A, Fernández-Campos MJ, Casado I, García-Rubira JC, García-Prieto J, Sanz-Rosa D, Cuellas C, Hernández-Antolín R, Albarrán A, Fernández-Vázquez F, de la Torre-Hernández JM, Pocock S, Sanz G, Fuster V. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial. Circulation. 2013 Oct 1;128(14):1495-503. doi: 10.1161/CIRCULATIONAHA.113.003653. Epub 2013 Sep 3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Lars Gullestad, Profesor, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT03004703    
Other Study ID Numbers: ASSAIL-MI 2.0
2016-002581-31 ( EudraCT Number )
First Posted: December 29, 2016    Key Record Dates
Last Update Posted: March 4, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lars Gullestad, Oslo University Hospital:
Interleukin 6
Tocilizumab
Acute coronary syndrome
STEMI
Inflammation
Additional relevant MeSH terms:
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Myocardial Infarction
Coronary Disease
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases