IL-6 Inhibition for Modulating Inflammation After Cardiac Arrest (IMICA)
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|ClinicalTrials.gov Identifier: NCT03863015|
Recruitment Status : Completed
First Posted : March 5, 2019
Last Update Posted : August 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Heart Arrest Out-Of-Hospital Cardiac Arrest Systemic Inflammatory Response Syndrome||Drug: Tocilizumab 20 Mg/mL Intravenous Solution Drug: isotonic saline||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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)|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest - a Randomized Clinical Trial|
|Actual Study Start Date :||March 4, 2019|
|Actual Primary Completion Date :||December 23, 2019|
|Actual Study Completion Date :||June 30, 2020|
Active Comparator: Tocilizumab
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
Tocilizumab is suspended in isotonic saline to a total volume of 100mL prior to infusion
Other Name: RoActemra
Placebo Comparator: Isotonic saline
A one hour infusion of isotonic saline
Drug: isotonic saline
A one hour infusion of 100mL isotonic saline
Other Name: Placebo
- Concentration of hsCRP [ Time Frame: Daily measurements from admission to 72 hours after admission. ]high sensitivity C-reactive protein
- Biomarkers of organ damage [ Time Frame: Plasma/serum samples and routine biochemistry are collected at admission, 24h, 48h and 72h (NSE only at 48 and 72h) ]
Markers of cerebral injury: Neuron-specific enolase (NSE) levels (routine biochemistry), and other markers of cerebral injury (analysis of samples in biobank).
Markers of cardiac injury: Troponin T (TnT) and CKMB levels. Markers of kidney injury: Creatinine levels. Markers of hepatic injury: ALAT, ASAT, bilirubin, INR. Markers of endothelial injury: soluble thrombomodulin levels.
- Markers of inflammation, interleukin levels [ Time Frame: At admission, 24h, 48h & 72h ]Interleukin levels: INF-g, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8 IL-10, IL-12, IL-13, IL-17A, G-CSF, GM-CSF, MCP-1 og MIP-1beta and TNF-α (analysis of samples in biobank).
- Markers of inflammation, leukocytes [ Time Frame: At admission, 24h, 48h & 72h ]Leukocyte differential count.
- Markers of inflammation, SOFA score [ Time Frame: The first 3 days from admission ]Daily Sequential Organ Failure Assessment (SOFA) scores.
- Markers of the coagulation system, fibrinogen [ Time Frame: At admission, 48h and 72h ]The possible downstream effect of dampened inflammation on the coagulation system is evaluated by the concentration of plasma-fibrinogen.
- Markers of the coagulation system, thrombelastography [ Time Frame: At admission and 48h ]The possible downstream effect of dampened inflammation on the coagulation system is evaluated by whole blood thrombelastography.
- Markers of hemodynamic function, Swan-Ganz Catheter [ Time Frame: At admission, 24h, 48h & 72h ]Swan-Ganz based measurements of cardiac output, central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance.
- Markers of hemodynamic function, Arterial blood gasses [ Time Frame: At admission, 2h, 4h, 6h, 8h, 10h, 12h, 18h, 24h, 30h, 36h, 48h, 72h, 96h and 120h (sampling ceases if the arterial line is discontinued). ]Arterial blood gasses including lactate and base excess at frequent intervals.
- Markers of hemodynamic function, Echocardiography [ Time Frame: Day 1 and on either day 3, 4 or 5. ]Transthoracic echocardiography including assesment of left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE).
- Clinical endpoints, Survival [ Time Frame: At 30 days, 90 days, 180 days, and at end of trial. ]Survival.
- Clinical endpoints, MOCA score [ Time Frame: At 90 days. ]Montreal Cognitive Assessment (MOCA) score at 90 days.
- Clinical endpoints, CPC [ Time Frame: At 30 days, 90 days and 180 days. ]Cerebral Performance Category (CPC) at 30 days, 90 days and 180 days, assessed by telephone interview and/or review of medical file after completion of the 180 days.
- Safety: incidence of adverse events [ Time Frame: From admission till 7 days. ]Cumulated incidence of adverse events the first 7 days.
- Predefined sub-study: MRI of heart and brain [ Time Frame: The day following admission. ]A subset of the trial participants will be enrolled in a sub-study focusing on cardio protection and neuroprotection as a pilot investigation. This sub-study will include an echocardiography, a cerebral MR scan and a cardiac MR scan; all three modalities being performed the day following admission.
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): NCT03863015
|Copenhagen, Denmark, 2100|
|Principal Investigator:||Christian Hassager, MD, DMSc||Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark|