IL-6 Inhibition for Modulating Inflammation After Cardiac Arrest

NCT03863015 | Completed Phase 2

• 1 other identifier: EudraCT:2018-002686-19
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Resuscitated cardiac arrest is associated with a systemic inflammatory response that is directly associated with poor prognosis. Inhibition of the IL-6 mediated immune response may potentially inhibit the systemic inflammatory response, potentially improving the prognosis of these severely ill patients.

Conditions

Heart Arrest; Out-Of-Hospital Cardiac Arrest; Systemic Inflammatory Response Syndrome

Keywords

OHCA; PCAS; SIRS; Inflammation; RoActemra; Tociluzumab

Outcome Measures

Primary Outcomes (1)

• Concentration of hsCRP

  high sensitivity C-reactive protein

  Daily measurements from admission to 72 hours after admission.

Secondary Outcomes (13)

• Biomarkers of organ damage

  Plasma/serum samples and routine biochemistry are collected at admission, 24h, 48h and 72h (NSE only at 48 and 72h)

• Markers of inflammation, interleukin levels

  At admission, 24h, 48h & 72h

• Markers of inflammation, leukocytes

  At admission, 24h, 48h & 72h

• Markers of inflammation, SOFA score

  The first 3 days from admission

• Markers of the coagulation system, fibrinogen

  At admission, 48h and 72h

Other Outcomes (1)

• Predefined sub-study: MRI of heart and brain

  The day following admission.

Study Arms (2)

Tocilizumab

ACTIVE COMPARATOR

A one hour infusion of a single 8mg/kg dose (max. 800mg) of tocilizumab to attenuate systemic inflammation after out-of-hospital cardiac arrest, given as early as possible after hospital admission.

Drug: Tocilizumab 20 Mg/mL Intravenous Solution

Isotonic saline

PLACEBO COMPARATOR

A one hour infusion of isotonic saline

Drug: isotonic saline

Interventions

Tocilizumab 20 Mg/mL Intravenous Solution DRUG

Tocilizumab is suspended in isotonic saline to a total volume of 100mL prior to infusion

Also known as: RoActemra

Tocilizumab

isotonic saline DRUG

A one hour infusion of 100mL isotonic saline

Also known as: Placebo

Isotonic saline

Eligibility Criteria

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

You may qualify if:

• Each of the following criteria must be fulfilled for a subject to be eligible:
• Age ≥ 18 years
• OHCA of a presumed cardiac cause
• Unconsciousness upon admission, i.e. a GCS \< 9
• Sustained ROSC for more than 20 minutes

You may not qualify if:

• None of the following criteria must be fulfilled for a subject to be eligible:
• Consciousness upon admission, i.e. a GCS ≥ 9
• Presumed non-cardiac cause of arrest
• Unwitnessed asystole
• Suspected or confirmed intracranial bleeding or stroke
• Temperature on admission \< 30 °C
• Known disease making 180 day survival unlikely
• Known limitations in therapy
• Known pre-arrest Cerebral Performance Category of 3 to 4
• \> 240 minutes from ROSC to randomization

Sponsors & Collaborators

• Christian Hassager: lead

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (28)

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• Meyer MAS, Wiberg S, Grand J, Meyer ASP, Obling LER, Frydland M, Thomsen JH, Josiassen J, Moller JE, Kjaergaard J, Hassager C. Treatment Effects of Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest (The IMICA Trial): A Double-Blinded, Placebo-Controlled, Single-Center, Randomized, Clinical Trial. Circulation. 2021 May 11;143(19):1841-1851. doi: 10.1161/CIRCULATIONAHA.120.053318. Epub 2021 Mar 22.

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• Meyer MAS, Wiberg S, Grand J, Kjaergaard J, Hassager C. Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial. Trials. 2020 Oct 20;21(1):868. doi: 10.1186/s13063-020-04783-4.

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MeSH Terms

Conditions

Heart Arrest; Out-of-Hospital Cardiac Arrest; Systemic Inflammatory Response Syndrome; Inflammation

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Christian Hassager, MD, DMSc

  Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

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 INVESTIGATOR
• PI Title: Professor, MD, DMSc, FESC

Model Details: Subjects will be randomized in a 1:1 fashion to receive IL-6RA or placebo. Patients being allocated to IL-6RA will receive a one-hour infusion of 8 mg tocilizumab per kg body weight (maximum dose 800 mg, 40 mL), equivalent to 0.4 mL per kg bodyweight (study drug concentration 20 mg/mL). Patients being allocated to placebo will receive a one-hour infusion of 0.4 mL /kg body weight of normal saline (maximum dose 40 mL)

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: March 5, 2019
• Study Start: March 4, 2019
• Primary Completion: December 23, 2019
• Study Completion: June 30, 2020
• Last Updated: August 21, 2020

Record last verified: 2020-08

Locations

DK (1)