EA-230 is a new therapy that may help people recover faster and have fewer problems after bypass surgery. In an earlier clinical trial, participants who received EA-230 during Coronary Artery Bypass surgery stayed in the Intensive Care Unit (ICU) and the hospital for a shorter time and had fewer serious complications, compared to those who received a placebo (an inactive therapy). The use of EA-230 was safe and well tolerated. This trial will test EA-230 in more participants to see if it really works and is safe to use in the future. This is a Phase III trial. It will take place in multiple locations and will follow a double-blind, randomized, placebo-controlled clinical design, meaning neither doctors nor participants will know whether they receive EA-230 or placebo during the trial. Assignment to EA-230 or placebo occurs by chance, like throwing dice. The total duration of the trial, including medical check-ups, will be approximately 71 days. There is a total of 10 visits, including a screening-, a pre-operative-, and 2 remote visits. 7 of these visits are during your stay at the hospital.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
300
Intravenous administration of 90mg/kg per hour for 4 hours.
Placebo administered intravenously for 4 hours
MAYO clinic
Rochester, Minnesota, United States
UZ Gent
Ghent, Belgium
Medisch Spectrum Twente
Enschede, Netherlands
RadboudUMC
Nijmegen, Netherlands
St Thomas' Hospital
London, United Kingdom
Required postoperative hospital length of stay
Median postoperative duration, from the moment of first incision until the time when a patient is eligible to be discharged from the hospital.
Time frame: Up to 28 days
Required postoperative ICU length of stay
Median postoperative duration, from the moment of first incision until the time when a patient is eligible to be discharged from the ICU and transferred to the general ward.
Time frame: Up to 28 days
Actual postoperative hospital length of stay
Median postoperative duration, from the moment of first incision until the time when a patient is actually discharged from the hospital.
Time frame: Up to 28 days
Actual postoperative ICU length of stay
Median postoperative duration, from the moment of first incision until the time when a patient is actually discharged from the ICU and transferred to the general ward.
Time frame: Up to 28 days
Single Organ Outcome Measures (SOOMs)
Median cumulative duration of moderate and severe Single Organ Outcome Measures (SOOMs) according to the European Perioperative Clinical Outcome (EPCO) definitions during the trial.
Time frame: Up to 28 days
Net Fluid Balance (NFB) in milliliters (mL)
Median cumulative NFB at the start of IMP administration (T0) and up to 24 and 48 hours thereafter. NFB is measured by the difference between a patient's total fluid intake and total fluid output. This includes all intravenous fluids, oral intake, and nutritional feeds against urine output, drainage, and other fluid losses. No correction is applied for insensible losses (e.g., sweating, or respiratory exhalation).
Time frame: Up to 2 days (48 hours) after start of surgery (first incision)
Vasopressor use in microgram per kilogram (µg/kg) and/or international units (IU)
Cumulative dose of vasopressors at the start of IMP administration (T0) and up to 24 and 48 hours thereafter.
Time frame: Up to 2 days (48 hours) after start of surgery (first incision)
Inotropic use in microgram per kilogram (µg/kg)
Cumulative dose of inotropes at the start of IMP administration (T0) and up to 24 and 48 hours thereafter.
Time frame: Up to 2 days (48 hours) after start of surgery (first incision)
Vasopressor-Inotropic Score
Vasopressor-inotropic score at the start of IMP administration (T0) and up to 24 and 48 hours thereafter. Vasoactive-Inotropic Score is calculated as follows: Dopamine dose (µg/kg/min) + Dobutamine dose (µg/kg/min) + 100 \* Epinephrine dose (µg/kg/min) + 100 \* Norepinephrine dose (µg/kg/min) + 100 \* Vasopressin dose (units/min) + 1000 \* Milrinone dose (µg/kg/min) + 2000 \* Levosimendan dose (µg/kg/min).
Time frame: Up to 2 days (48 hours) after start of surgery (first incision)
Blood plasma levels of EA-230 in microgram per liter (µg/L)
Blood plasma levels of EA-230 measured immediately before the end of EA-230 infusion (T4) in all patients. Blood plasma levels of EA-230 measured at T0, T0.5, T1, T2, T3 and T4 in a subset of patients in the Netherlands. Only venous blood is sampled to determine blood plasma levels.
Time frame: Up to 4 hours after IMP administration (on Day 1)
Treatment emergent (Serious) Adverse Events and Adverse Drug Reactions
Incidence of treatment emergent (Serious) Adverse Events and Adverse Drug Reactions during the trial period. Coded using the Medical Dictionary for Regulatory Activities (version 28 or higher) and graded according to the Common Terminology Criteria for Adverse Events (V6.0).
Time frame: Up to 28 days
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