Clinical trial NCT06425614: COmbined pLaTelet and eRythrocyte AutotransfusioN During Cardiac surgEry (COLTRANE) Trial
Official title: Centrifugation-based Versus Filtration-based Intraoperative Cell Salvage on Quality of Perioperative Haemostasis in Cardiac Surgery: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: On-pump Cardiac Surgery
High Risk for Bleeding
Autotransfusion
Keywords: cardiac surgery
bleeding
autotransfusion
cardiopulmonary bypass
perioperative haemostasis
Universal Definition of Perioperative Bleeding
filtration-based autotransfusion
centrifugation-based autotransfusion
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2024-05-22
Enrollment: 570
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre clinical trial, Randomized, Comparative, controlled, single blinded, superiority design, two groups.
Primary purpose: OTHER

Brief summary: Despite significant advances in patient blood management, cardiac surgery remains a surgical procedure at high risk for bleeding. Numerous perioperative blood conservation strategies have been developed for limiting the use of blood products. Among them, the processing of shed blood and residual cardiopulmonary bypass circuit volume with autotransfusion device is routinely used. Conventional centrifugation-based autotransfusion devices actually available only recover red blood cells while platelets and coagulation factors are almost totally lost. Consequently, large amounts of intraoperative cell salvage could significantly alter perioperative haemostasis. The SAME autotransfusion device (i-SEP, France) is a new and innovative filtration-based autotransfusion device able to recover erythrocytes, leukocytes but also platelets. By offering the opportunity to re-infuse to patients their own platelets in addition red blood cells, significantly improve perioperative haemostasis with this new device is expected. The purpose of the COLTRANE trial is to compare the quality of the perioperative haemostasis in cardiac surgical patients for whom intraoperative cell salvage will be performed using either the SAME autotransfusion device or conventional centrifugation-based device.

Because allogenic transfusion of blood products as well as surgical re-exploration for excessive bleeding are associated with poor outcomes and prolonged length of stay, the use of filtration-based SAME device by maintaining perioperative haemostasis could improve outcomes and reduce length of stay of high risk patients. The fact that patients receive their own platelets should also limit the risk of allo-immunization and immunomodulation which is recognized as one of the underlying mechanisms of perioperative increased risk of infection.

Detailed description: The SAME device is a new and innovative filtration-based autotransfusion device able to recover both erythrocytes and platelets. A multicentre single-arm clinical feasibility and safety trial conducted by our group, using SAME device on 50 cardiac surgical patients reported erythrocyte yield per cycle of 89%, post-treatment hematocrit of 43% with an excellent washing performance. In addition, the device recovered 52% of platelets, that were found unaltered by the device as demonstrated by a limited platelet activation and a strong response to thrombin-pathway stimulation assessed by flow cytometry. By offering the opportunity to re-infuse to the patients their own platelets in addition to their RBC, this new device might significantly improve perioperative haemostasis and thus decrease the need for blood products. It is well established that severe postoperative bleeding and blood products transfusion lead to increase morbidity and mortality. Consequently, an improvement of postoperative outcomes and a decrease in intensive care unit (ICU) and hospital length of stay may be expected. The fact that patients receive their own platelets should limit the risk of allo-immunization and immunomodulation which is recognized as one of the underlying mechanisms of perioperative increased risk of infection. Consequently, a reduction of infectious complication may be also expected.

The purpose of COLTRANE trial is to test the hypothesis that the intraoperative use of the filtration-based SAME autotransfusion device could improve perioperative haemostasis thereby reducing the proportion of patients exhibiting clinically significant perioperative bleeding (moderate to massive bleeding according the Universal Definition of Perioperative Bleeding (UDPB) classification).

Eligibility criteria: Inclusion Criteria:

Adult patients (≥18 yr) affiliated or beneficiary of a social security scheme and undergoing on-pump cardiac surgery at high risk for bleeding with autotranfusion indication defined as:

* Primary or redo combined cardiac procedures (2 valves or more, valve(s) and coronary artery bypass grafting(s))
* Primary or redo ascending aorta surgery
* Primary or redo isolated coronary artery bypass grafting (iCABG) involving 3 or more grafts using the internal mammary artery
* Free, informed and written consent signed by the participant and the investigator

Exclusion Criteria:

* Preoperative therapy by P2Y12 receptor inhibitors (within 5 preoperative days for clopidogrel, ticagrelor or ticlopidine, within 7 preoperative days for prasugrel, and within one preoperative hour for cangrelor)
* Preoperative treatment by active anticoagulant drug (within 5 preoperative days for VKA, 4 days for dabigatran, 3 days for rivaroxaban and apixaban, 24 hours for therapeutic LMWH, 36 hours for therapeutic fondaparinux, 12 hours for prophylactic LMWH, 24 hours for prophylactic fondaparinux, 4 hours for unfractionated heparin Sepsis
* Malignant tumor
* Immunocompromised patients (steroids, immunosuppressive drugs, ongoing treatment for solid tumor or hematologic malignancy, primary immunodeficiency disorders, AIDS)
* Emergency cardiac surgery
* Heart transplantation
* Implantation or patients under ventricular assist device (VAD)
* Patients with two or more previous sternotomy
* Surgery procedure requiring circulatory arrest and/or profound hypothermia (\<32°C)
* Active infective endocarditis
* Cardiac surgical procedure for benign or malignant cardiac tumors
* Patients with known acquired or constitutional coagulopathy requiring specialist management
* End stage renal disease
* Preoperative haemoglobin level less than 10 g/dL
* Preoperative platelet count \< 100 G/L
* Persons participating in another interventional research including a period of exclusion that is still ongoing
* Pregnant or breastfeeding women
* Persons placed under judicial protection
* Patients deprived of liberty

Primary outcomes:
measure: Perioperative bleeding
timeFrame: At the end of Day 1
Secondary outcomes:
measure: total blood loss
timeFrame: Hours 12, Hours 24, up to 5 after operatives days
measure: surgical re-exploration
timeFrame: Day 0-Day 5,
measure: Sternal closure
timeFrame: Hours 12
measure: Overall quality of perioperative haemostasis : Use of blood
timeFrame: Day 0-Day 2,
measure: Perioperative biological hemostasis
timeFrame: Pre-inclusion - Day 5
measure: Complete blood count
timeFrame: Pre-inclusion - Day 5
measure: ICU and hospital length of stay
timeFrame: End of study or early termination- Day 30
measure: Early postoperative morbidity within 30 postoperative days
timeFrame: Day 30
Other outcomes:
measure: COST-BENEFIT
timeFrame: Day 30 /+2 days
measure: Haemoglobin and plasma free haemoglobin
timeFrame: just before surgery as well as 6+/-2 hours after surgery
measure: Hematocrit
timeFrame: During the surgery
measure: Complete blood count
timeFrame: During the surgery
measure: Unfractionated heparin anti-Xa
timeFrame: During the surgery
measure: Fibrinogen
timeFrame: During the surgery
measure: Triglycerides
timeFrame: During the surgery
measure: Total proteins
timeFrame: During the surgery
measure: Potassium
timeFrame: During the surgery
measure: Blood viscoelasticity assessment
timeFrame: just before and immediately after re-infusion, pré-treatment and just after traitement by the autotransfusion device
measure: Complete bloof count
timeFrame: just before and immediately after re-infusion, pré-treatment and just after traitement by the autotransfusion device
measure: INF-γ profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
measure: IL-1β-γ profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
measure: Il-6 profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
measure: IL-8 profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
measure: IL-10 profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
measure: TNFα profiling by mass cytometry CyTOF
timeFrame: just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux, Hôpital cardiologique Haut Lévêque - GH Sud, Service Anesthésie Réanimation Cardiovasculaire
city: Bron
country: France
facility: HOSPICES CIVILS DE LYON, Hôpital Louis Pradel, Service Anesthésie Réanimation
city: Montpellier
country: France
facility: CHU MONTPELLIER, Hôpital Arnaud de Villeneuve, Service Anesthésie Réanimation Arnaud de Villeneuve
city: Nantes
country: France
facility: CHU Nantes, Service Anesthésie Réanimation de chirurgie cardiaque
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpêtrière, APHP, Service Anesthésie Réanimation chirurgicale
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard, APHP, Service Anesthésie Réanimation
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou, AP-HP, Service Anesthésie Réanimation
city: Rennes
country: France
facility: CHU Rennes, Hôpital Pontchaillou, Service Anesthésie Réanimation 3-Réanimation CTCV
city: Strasbourg
country: France
facility: CHRU STRASBOURG, Nouvel Hôpital Civil, Service Anesthésie Réanimation chirurgicale
city: Toulouse
country: France
facility: CHU Toulouse, Hôpital Rangueil, Service Anesthésie
Study officials:
affiliation: University Hospital, Bordeaux
name: Alexandre Ouattara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: