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

Overview

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).

Interventions

• Procedure Autotransfusion
  ANTIFIBRINOLYTIC THERAPY : tranexamic acid as antifibrinolytic therapy : dose after anaesthesia induction followed by continuous intravenous infusion until end INTRAOPERATIVE MANAGEMENT : * Routine monitoring : five lead-ECG, pulse oximeter, non-invasive arterial pressure will be instituted. A peripheral venous catheter and an arterial catheter * The general anaesthesia : * propofol and Remifentanil or sufentanil both simultaneously administered . * monitoring of the bispectral index * Triple

Primary outcome measures

• Perioperative bleeding [Time frame: At the end of Day 1]

Secondary outcome measures (8)

• total blood loss [Time frame: Hours 12, Hours 24, up to 5 after operatives days]
• surgical re-exploration [Time frame: Day 0-Day 5,]
• Sternal closure [Time frame: Hours 12]
• Overall quality of perioperative haemostasis : Use of blood [Time frame: Day 0-Day 2,]
• Perioperative biological hemostasis [Time frame: Pre-inclusion - Day 5]
• Complete blood count [Time frame: Pre-inclusion - Day 5]
• ICU and hospital length of stay [Time frame: End of study or early termination- Day 30]
• Early postoperative morbidity within 30 postoperative days [Time frame: Day 30]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Other

Study locations

France · 10 centers

• CHU de Bordeaux, Hôpital cardiologique Haut Lévêque - GH Sud, Service Anesthésie Réanimati — Bordeaux
• HOSPICES CIVILS DE LYON, Hôpital Louis Pradel, Service Anesthésie Réanimation — Bron
• CHU MONTPELLIER, Hôpital Arnaud de Villeneuve, Service Anesthésie Réanimation Arnaud de Vi — Montpellier
• CHU Nantes, Service Anesthésie Réanimation de chirurgie cardiaque — Nantes
• Groupe Hospitalier Pitié Salpêtrière, APHP, Service Anesthésie Réanimation chirurgicale — Paris
• Hôpital Bichat-Claude Bernard, APHP, Service Anesthésie Réanimation — Paris
• Hôpital Européen Georges Pompidou, AP-HP, Service Anesthésie Réanimation — Paris
• CHU Rennes, Hôpital Pontchaillou, Service Anesthésie Réanimation 3-Réanimation CTCV — Rennes
• … and 2 more centers

Publications

• Beurton A, Mansour A, Benard A, Pernot M, Brett VE, Batsale C, Aitgougam A, Cordon A, Mouton C, Fresselinat A, Robert G, Imbault J, Nesseler N, Ouattara A. Centrifugation versus filtration-based cell salvage: impact on perioperative bleeding in cardiac surgery-the COLTRANE randomised clinical trial - study protocol. BMJ Open. 2025 Jul 16;15(7):e099423. doi: 10.1136/bmjopen-2025-099423. PMID 40669902

Identifiers

NCT: NCT06425614 · CHUBX 2022/22 · 2022-A02566-39

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗