COmbined pLaTelet and eRythrocyte AutotransfusioN During Cardiac surgEry (COLTRANE) Trial

Not Applicable

Recruiting

• Conditions: On-pump Cardiac Surgery; Autotransfusion; High Risk for Bleeding
• Interventions: Procedure: Autotransfusion

• Registration Number: NCT06425614
• Lead Sponsor: University Hospital, Bordeaux

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).

Study Timeline

• Study First Submitted: 2024-01-12
• Study First Submitted QC: 2024-05-17
• Study First Posted: 2024-05-22
• Status Verified: 2024-07
• Study Start: 2024-07-15
• Last Update Submitted: 2024-07-17
• Last Update Posted: 2024-07-19
• Primary Completion: 2026-02-15
• Study Completion: 2026-02-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 570

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Autotransfusion by centrifugation	Autotransfusion	centrifugation-based autotransfusion (routinely used in cardiac surgery centers)
Autotransfusion by filtration	Autotransfusion	new filtration-based autotransfusion (SAME I-SEP device)

Primary Outcome Measures

Name	Time	Method
Perioperative bleeding	At the end of Day 1	The proportion of patients with clinically significant (moderate to massive) perioperative bleeding according to the Universal Definition for Perioperative Bleeding.

Secondary Outcome Measures

Name	Time	Method
surgical re-exploration	Day 0-Day 5,	Surgical re-exploration for excessive bleeding within 5 postoperative days
Sternal closure	Hours 12	Delayed sternal closure
Overall quality of perioperative haemostasis : Use of blood	Day 0-Day 2,	Perioperative use of blood products and/or plasma derivatives within 2 postoperative days including PRBC, PLT, FFP, fibrinogen concentrate, PCCs, rFVIIa
Perioperative biological hemostasis	Pre-inclusion - Day 5	Coagulation tests (PT, aPTT, fibrinogen level) preoperatively, at the end of the surgery (+ thrombin time or ACT ), at arrival in ICU and at POD1, 3 and 5
ICU and hospital length of stay	End of study or early termination- Day 30	calculated ICU and hospital free days
Early postoperative morbidity within 30 postoperative days	Day 30	Cardiovascular: need for inotropes and/or vasopressors intravenous infusion \>24 hours, need for short-term mechanical circulatory support, occurrence of atrial fibrillation and/or ventricular fibrillation/tachycardia, high grade atrioventricular bloc, myocardial infarction, tamponade, symptomatic thromboembolic events.; Respiratory: duration of mechanical ventilation, re-intubation, ARDS according the Berlin criteria, need for VV ECMO Renal: Kidney Disease Improving Global Outcomes stage (KDIGO) ≥2; need for renal replacement therapy. Serum electrolytes and renal function preoperatively, at arrival in ICU and at POD1, 3 and 5.; Neurology: transient and permanent stroke, epilepsy, confusion Infectious: mediastinitis, septic shock, pneumopathy and bacteremia Abdominal: mesenteric ischemia, upper and/or lower gastrointestinal bleeding. Liver function tests preoperatively, at arrival in ICU and at POD1, 3 and 5.; 30-day all-cause mortality
total blood loss	Hours 12, Hours 24, up to 5 after operatives days	Total blood loss from chest tubes within 12 and 24 postoperative hours and up to chest tubes removal (maximum 5 postoperative days)
Complete blood count	Pre-inclusion - Day 5	Complete blood count preoperatively, at the end of the surgery, at arrival in ICU and at POD1, 3 and 5.

Trial Locations

Locations (10)

CHU de Bordeaux, Hôpital cardiologique Haut Lévêque - GH Sud, Service Anesthésie Réanimation Cardiovasculaire; 🇫🇷 Bordeaux, France

HOSPICES CIVILS DE LYON, Hôpital Louis Pradel, Service Anesthésie Réanimation; 🇫🇷 Bron, France

CHU MONTPELLIER, Hôpital Arnaud de Villeneuve, Service Anesthésie Réanimation Arnaud de Villeneuve; 🇫🇷 Montpellier, France

CHU Nantes, Service Anesthésie Réanimation de chirurgie cardiaque; 🇫🇷 Nantes, France

Groupe Hospitalier Pitié Salpêtrière, APHP, Service Anesthésie Réanimation chirurgicale; 🇫🇷 Paris, France

Hôpital Bichat-Claude Bernard, APHP, Service Anesthésie Réanimation; 🇫🇷 Paris, France

Hôpital Européen Georges Pompidou, AP-HP, Service Anesthésie Réanimation; 🇫🇷 Paris, France

CHU Rennes, Hôpital Pontchaillou, Service Anesthésie Réanimation 3-Réanimation CTCV; 🇫🇷 Rennes, France

CHU Toulouse, Hôpital Rangueil, Service Anesthésie; 🇫🇷 Toulouse, France

CHRU STRASBOURG, Nouvel Hôpital Civil, Service Anesthésie Réanimation chirurgicale; 🇫🇷 Strasbourg, France