Coronary Artery Bypass Graft Surgery(CABG), Coronary Artery Disease (CAD)
Conditions
Brief summary
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.
Detailed description
The sites and vendor have been selected, and no further engagement regarding acquisition will be considered.
Interventions
DRUGEA-230 90mg/kg/hour
Intravenous administration of 90mg/kg per hour for 4 hours.
DRUGPlacebo
Placebo administered intravenously for 4 hours
Sponsors
EBI Anti Sepsis BV
CR2O B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled Phase III Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥18 years, both male and female. 2. Patients scheduled for elective on-pump CABG with at least 3 bypasses, with or without valve replacement. 3. Willing and able to give written informed consent.
Exclusion criteria
1. Patients undergoing non-elective on-pump CABG (i.e., emergency surgery). Emergency surgery is defined as planned surgery within 24 hours of diagnosis. 2. Cardiogenic shock or hemodynamic instability that requires inotropes, vasopressors, or other mechanical devices, such as an intra-aortic balloon counter-pulsation (IABP), within 24 hours prior to surgery. 3. Use of a left ventricular assist device (LVAD), or intra-aortic balloon pump or other cardiac devices, within 7 days prior to surgery. 4. A requirement for any of the following within 7 days prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, or other forms of mechanical circulatory support. 5. Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery. 6. Known chronic liver disorder with Child-Pugh C classification. 7. Confirmed or treated endocarditis requiring antimicrobial or antiviral treatment within 30 days prior to surgery or other current active infection requiring antimicrobial or antiviral treatment within 14 days prior to surgery. 8. Ongoing sepsis (as defined by SEPSIS-3) within 2 weeks of screening or, in the opinion of the investigator, an untreated clinically significant infection (viral or bacterial) prior to or at Screening and before randomization. 9. Immuno-compromised patients, as self-reported or as observed in medical records, including patients: 1. with solid organ transplantation. 2. known to be positive for human immunodeficiency virus (HIV). 3. that use immunosuppressive drugs or have received recent chemotherapy, at the discretion of the Investigator and including patients; i. with active malignancy who have undergone chemotherapy within 30 days prior to trial entry. ii. receiving chronic corticosteroid treatment equivalent to a prednisone dose of 10 mg or higher per day, within 30 days prior to trial entry, or an equivalent dose of another corticosteroid or any other anti-inflammatory or inflammation-suppressing medications such as interleukin blockers, methotrexate or similar therapies. Non-Steroidal Anti-Inflammatory Drugs are not exclusionary. 10. Patients with hematological disorders (known disorders from myeloid and/or lymphoid origin, leucopenia (both active and in remission)). 11. Known severe renal disease requiring dialysis, or a known estimated Glomerular Filtration Rate (eGFR) prior to admission of \< 20 ml/min/1.73 m2. 12. Previous receipt of EA-230. 13. Known hypersensitivity to the IMP. 14. Use of any investigational drug within 1 month or 5 half-lives of said investigational drug (whichever is longer) prior to IMP administration in this trial. Participation in an observational clinical trial is not exclusionary. 15. Women who are pregnant, breastfeeding or planning to become pregnant during the trial or within 28 days after IMP administration (WOCBP must have a negative pregnancy test prior to entry into the trial). 16. Female patients of childbearing potential who are not willing/able to use adequate contraception and refrain from donating ova from enrolment and up to 28 days after IMP administration (contraceptive requirements are detailed in Annex 5. Contraceptive Guidance). 17. Male patients who are not willing/able to use adequate contraception (if their partners is of childbearing potential) and refrain from donating sperm from enrolment and up to 28 days after IMP administration (contraceptive requirements are detailed in Annex 5. Contraceptive Guidance). 18. Inability to personally provide written informed consent. 19. Known or suspected of not being able to comply with the trial protocol, at the discretion of the Investigator. 20. Any other condition which, in the Investigator's opinion, will interfere with completion of the trial. 21. Being an employee of the Investigator or trial site with direct involvement in the proposed trial or other studies under the direction of that Investigator or trial site or being a family member of an employee of the Investigator with direct involvement in the proposed trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Required postoperative hospital length of stay | Up to 28 days | Median postoperative duration, from the moment of first incision until the time when a patient is eligible to be discharged from the hospital. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the effect of EA-230 on the duration of moderate and severe POCs | Up to 28 days | Median cumulative duration of moderate and severe Single Organ Outcome Measures (SOOMs) according to the European Perioperative Clinical Outcome (EPCO) definitions during the trial. |
| Hemodynamic stability via Net fluid balance | Up to 2 days (48 hours) after start of surgery (first incision) | Median cumulative Net fluid balance (NFB) at the start of IMP administration (T0) and up to 24 and 48 hours thereafter. |
| Hemodynamic stability via VIS score | Up to 2 days (48 hours) after start of surgery (first incision) | Cumulative dose of vasopressors and inotropes used and vasopressor-inotropic scores at the start of IMP administration (T0) and up to 24 and 48 hours thereafter, compared between treatment arms. Up to 2 days (48 hours) after start of surgery (first incision) |
| Required postoperative ICU length of stay | Up to 28 days | 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. |
| Actual postoperative ICU and hospital length of stay | Up to 28 days | Median postoperative duration, from the moment of first incision until the time when a patient is actually discharged from the ICU, and discharged from the hospital |
| Blood plasma levels of EA-230 in microgram per liter (µg/L) | Up to 4 hours after IMP administration (on Day 1) | 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. |
| Safety assessment of EA-230 | Up to 28 days | 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). |
Countries
Belgium, Netherlands, United Kingdom, United States
Contacts
CONTACTBas Ossenkoppele, Msc
CONTACTLeonie Koomen, Msc
PRINCIPAL_INVESTIGATORPeter Pickers, Prof.
Radboudmc
Outcome results
None listed