Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE December 20, 2016
First Posted Date  ICMJE December 29, 2016
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE March 16, 2017
Actual Primary Completion Date February 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 23, 2016)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2016)
  • The between-group difference in the AUC for Troponin T (TnT) during index hospitalisation [ Time Frame: 24 -72 hours after randomisation ]
  • The extent of microvascular obstruction as measured by CMR after 3 - 7 days [ Time Frame: 3 - 7 days after randomisation ]
  • Final infarct size as measured by CMR 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  • Left ventricular size as assessed by CMR 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  • Baseline-adjusted NT-proBNP at 6 months after randomisation [ Time Frame: 6 months after randomisation ]
  • The AUC of Creatine Kinase-MB (CK-MB) during index hospitalisation [ Time Frame: 24-72 hours after randomisation ]
  • The AUC of C-reactive protein (CRP) during index hospitalisation [ Time Frame: 24-72 hours after randomisation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial
Official Title  ICMJE ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Disease
  • Myocardial Infarction
Intervention  ICMJE
  • 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®,
  • Drug: Sodium chloride 0.9%
    Placebo: Sodium chloride 0.9%; 100 ml i.v. once.
    Other Name: NaCl 0.9%
Study Arms  ICMJE
  • Experimental: Active drug
    Tocilizumab, 20 mg/ml; 14 ml (280 mg) dissolved in 100 ml NaCl 0.9 % i.v. once.
    Intervention: Drug: Tocilizumab
  • Placebo Comparator: Placebo
    Sodium chloride 0.9%; 100 ml i.v. once.
    Intervention: Drug: Sodium chloride 0.9%
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 23, 2016)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2020
Actual Primary Completion Date February 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03004703
Other Study ID Numbers  ICMJE ASSAIL-MI 2.0
2016-002581-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Undecided
Responsible Party Lars Gullestad, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE
  • St. Olavs Hospital
  • South-Eastern Norway Regional Health Authority
  • University of Oslo
  • Norwegian University of Science and Technology
Investigators  ICMJE
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
PRS Account Oslo University Hospital
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP