Cardiac Surgery
Conditions
Brief summary
Cardiac surgery is at high risk of intraoperative bleeding. Inhibitors of the P2Y12 platelet receptor, such as ticagrelor, are recommended in patients with acute coronary stroke (ACS) to reduce the incidence of major cardiovascular events. Nevertheless, some patients may require coronary artery bypass graft under cardiac bypass after ticagrelor administration. This administration within 48 hours prior to surgery is associated with a significant increase in bleeding and related poor outcomes, notably because platelet transfusion fails to reverse ticagrelor induced platelet dysfunction. Conversely, waiting several days to plan surgery, in the idea of clearing blood from ticagrelor, exposes to a risk of ischemic recurrence. Another situation where ticagrelor administration may impend prognosis is emergent aortic surgeries, including aortic dissection or aneurysm rupture. Ticagrelor is frequently administrated because symptoms can mimic ACS, but it may increase bleeding and transfusion by at least 50%. Several case reports and cohorts described blood hemadsorption, using the Cytosorb® blood purification system (Cytosorb®ents, USA) as a reversal therapy for ticagrelor, reducing bleeding. Cytosorb® is a polymeric beads system with a large exchange surface, enabling the adsorption and removal of molecules of intermediate sizes (\< 60 kDa). It has been described to reduce the plasma levels of ticagrelor, with a removal up to 75% after 60 min. It can be connected directly to the heart-lung machine. Its use during cardiac bypass is simple and has not described to induce additional hemolysis. We hypothesize that the use of Cytosorb® hemoadsorption during cardiac bypass would reduce the incidence of moderate to massive bleeding in patients receiving ticagrelor within 48 hours prior to surgery.
Interventions
DEVICEDevice: Cytosorb hemoadsorption
The Cytosorb® hemoadsorption cartridge is inserted into the cardiopulmonary bypass circuit immediately after the blood pump, with blood returned to the venous reservoir.
DEVICEDevice: Sham extracorporeal circuit
A sham tubing line, made of the same polymer and with the same diameter as the Cytosorb® tubing, is connected at the same location in the cardiopulmonary bypass circuit without a hemoadsorption cartridge.
Sponsors
University Hospital, Rouen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient or patient's representative having read and understood the information letter and signed the consent form 2. Age ≥ 18 y/o 3. Ticagrelor administration within 48 hours prior to surgery 4. Cardiac surgery with cardiac bypass 5. Patient affiliated with, or beneficiary of a social security (health insurance) category. 6. Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile): 1. with effective contraception (Cf. CTCG) (progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) since 1 month, during study period 2. negative blood pregnancy test by b-HCG at inclusion. 7. Women permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) 8. Postmenopausal women: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Exclusion criteria
1. Concomitant antiplatelet drugs or ongoing anticoagulants other than aspirin and heparin 2. Ongoing systemic infection (including active endocarditis) 3. Ongoing treatment with an antibiotic or antifungal at high risk of removal by Cytosorb®: teicoplanin, vancomycin, linezolid, gentamycin, amphotericin B liposomal, azole drugs or fluconazole 4. Ongoing treatment with an anticonvulsant at high risk of removal by Cytosorb®: phenytoin, phenobarbital or valproic acid. 5. Contraindications to Cytosorb® (known preoperative platelet count \< 20 000/mm3, Sickle cell disease crisis, history to heparin-induced thrombopenia, body mass index ≥ 40 kg/m², hypersensitivity to a component, Any pre-existing contraindication to extracorporeal therapy (CPB)) 6. Cardiac surgery for ventricle assistance device or transplantation 7. Preoperative critical state 8. Chronic pathology with life expectancy less than 1 month 9. Pregnant or breastfeeding women and women of child-bearing age not using effective means of contraception 10. Absence of affiliation to a social security program 11. Person deprived of liberty by an administrative or judiciary decision or person placed under judicial protection, under guardianship or supervision 12. Person consenting to the research participating having participated to another trial within a period of one week 13. Person participating to another interventional research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| benefit of Cytosorb® in reducing perioperative bleeding of cardiac surgery | within the 48 first hours post-CPB | Incidence of a moderate, severe or massive bleeding defined by an UDPB (Universal Definition for Perioperative Bleeding) score ≥ 2/4 within the 48 first hours post-CPB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| compare the distribution of bleeding severity between groups | 48 hours after surgery | Bleeding severity categorized according to the four-level UDPB classification within 48 hours post-CPB |
| compare the intensity of intraoperative bleeding | 48 hours after surgery | The validated intraoperative bleeding severity scale defined by Lewis et al (Surgery 2017, doi: 10.1016/j.surg.2016.09.022) The Lewis bleeding severity scale is scored based on visual assessment as follows: 0 = no bleeding 1. = ooze or intermittent flow 2. = continuous flow 3. = controllable spurting and/or overwhelming flow 4. = unidentified or inaccessible spurting or gush Based on anatomic appearance, it is scored from 0 (no bleeding) to 4 (central arterial- or venous-like bleeding). Based on qualitative description, it ranges from 0 (no bleeding) to 4 (life-threatening bleeding). Based on visually estimated rate of blood loss (mL/min), it is scored from 0 (≤1 mL/min) to 4 (\>50 mL/min). Although the scale includes four subscales, a single overall subjective score ranging from 0 to 4 is assigned based on the combined interpretation of all subscales. |
| compare the surgical reintervention rate due to bleeding between groups | 90 days | A surgical reintervention for any cause will be considered within 90 days. |
| compare between groups, the risk of other hemorrhagic complications | 90 days | Other hemorrhagic complications, including intracranial |
| compare between groups the risk of major adverse cardiovascular events | 90 days | The Major adverse cardiovascular events is defined as the composite outcome of myocardial infarction, cerebral stroke, acute heart failure, death |
| compare between groups, the risk of any complication in the composite outcome of acute kidney injury | 90 days | AKI will be defined as KDIGO ≥ 1; Acute respiratory failure will be defined by prolonged mechanical ventilation \> 12 hours, reintubation, non-invasive ventilatory support or high flow nasal cannula therapy;Infection, sepsis and septic shock, will be defined by the 2026 surviving sepsis campaign |
| compare quality of life between groups | 90 days | The EQ-5D-5L has 5 items with 5 likert levels leading to a score between 0% and 100% based on a specific population-dependent algorithm Higher scores indicate better quality of life (100% = very good health) |
| Red blood cell transfusion at 90 days | Baseline to 90 days | Total number of red blood cell (RBC) units transfused within 90 days after baseline. |
| Fresh frozen plasma transfusion at 90 days | Baseline to 90 days | Total number of fresh frozen plasma (FFP) units transfused within 90 days after baseline. |
| Prothrombin complex concentrate use at 90 days | Baseline to 90 days | Total dose of Prothrombin Complex Concentrate (PCC) administered within 90 days after baseline, reported in international units (IU). |
| Platelet transfusion at 90 days | Baseline to 90 days | Total number of platelet units transfused within 90 days after baseline. |
| Fibrinogen concentrate administration at 90 days | Baseline to 90 days | Total dose of fibrinogen concentrate administered within 90 days after baseline, reported in grams (g). |
| Activated factor VII administration at 90 days | Baseline to 90 days | Total dose of activated factor VII administered within 90 days after baseline, reported in grams (g). |
Countries
France
Contacts
CONTACTBESNIER
Outcome results
None listed