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

Centrifugation-based Versus Filtration-based Intraoperative Cell Salvage on Quality of Perioperative Haemostasis in Cardiac Surgery: A Randomized Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: On-pump Cardiac Surgery; High Risk for Bleeding; Autotransfusion
• Intervention / Treatment: Procedure: Autotransfusion

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 Type: Interventional
• Enrollment (Estimated): 570
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandre Ouattara, MD, PhD; Phone Number: +33 0557656866; Email: alexandre.ouattara@chu-bordeaux.fr
• Study Contact Backup: Name: Antoine Beurton, MD; Phone Number: 0557677147; Email: antoine.beurton@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux, Hôpital cardiologique Haut Lévêque - GH Sud, Service Anesthésie Réanimation Cardiovasculaire
    • Contact: Alexandre Ouattara, MD, PhD; Phone Number: +33 0557656866; Email: alexandre.ouattara@chu-bordeaux.fr
    • Contact: Antoine BEURTON; Phone Number: +33 0557656866; Email: antoine.beurton@chu-bordeaux.fr
  • Bron, France, 69677
    • HOSPICES CIVILS DE LYON, Hôpital Louis Pradel, Service Anesthésie Réanimation
    • Contact: Jean-Luc FELLAHI, MD, PhD; Phone Number: 0472118933; Email: jean-luc.fellahi@chu-lyon.fr
  • Montpellier, France, 34295
    • CHU MONTPELLIER, Hôpital Arnaud de Villeneuve, Service Anesthésie Réanimation Arnaud de Villeneuve
    • Contact: Philippe GAUDARD, MD; Phone Number: 0467336733; Email: p-gaudard@chu-montpellier.fr
  • Nantes, France, 44093
    • CHU Nantes, Service Anesthésie Réanimation de chirurgie cardiaque
    • Contact: Bertrand ROZEC, MD, PhD; Phone Number: 0240165304; Email: bertrand.rozec@chu-nantes.fr
  • Paris, France, 75651
    • Groupe Hospitalier Pitié Salpêtrière, APHP, Service Anesthésie Réanimation chirurgicale
    • Contact: Aude Carillion, MD; Phone Number: 0184827387; Email: aude.carillion@aphp.fr
  • Paris, France, 75877
    • Hôpital Bichat-Claude Bernard, APHP, Service Anesthésie Réanimation
    • Contact: Sophie Provenchere, MD; Phone Number: 0140258355; Email: sophie.provenchere@aphp.fr
  • Paris, France, 75908
    • Hôpital Européen Georges Pompidou, AP-HP, Service Anesthésie Réanimation
    • Contact: Bernard Cholley, MD, PhD; Phone Number: 0156092515; Email: bernard.cholley@aphp.fr
  • Rennes, France, 35033
    • CHU Rennes, Hôpital Pontchaillou, Service Anesthésie Réanimation 3-Réanimation CTCV
    • Contact: Alexandre Mansour, MD; Phone Number: 0299289153; Email: alexandre.mansour@chu-rennes.fr
  • Strasbourg, France, 67091
    • CHRU STRASBOURG, Nouvel Hôpital Civil, Service Anesthésie Réanimation chirurgicale
    • Contact: Paul-Michel MERTES, MD, PhD; Phone Number: 0369550444; Email: paul-michel.mertes@chru-strasbourg.fr
  • Toulouse, France, 31400
    • CHU Toulouse, Hôpital Rangueil, Service Anesthésie
    • Contact: François Labaste, MD; Phone Number: 0561322822; Email: labaste.f@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autotransfusion by filtration; new filtration-based autotransfusion (SAME I-SEP device)	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 lumen central venous catheter; Heparinization (300 UI/kg); Aortic and right auricular cannulations TRANSFUSION PROTOCOL : During CPB, PRBC transfusion if necessary; In the postoperative period if necessary In bleeding patients: The perioperative use of blood products will be managed according to results of conventional haemostasis tests or viscoelastic point of care tests when available in the center.
Other: Autotransfusion by centrifugation; centrifugation-based autotransfusion (routinely used in cardiac surgery centers)	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 lumen central venous catheter; Heparinization (300 UI/kg); Aortic and right auricular cannulations TRANSFUSION PROTOCOL : During CPB, PRBC transfusion if necessary; In the postoperative period if necessary In bleeding patients: The perioperative use of blood products will be managed according to results of conventional haemostasis tests or viscoelastic point of care tests when available in the center.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
total blood loss	Total blood loss from chest tubes within 12 and 24 postoperative hours and up to chest tubes removal (maximum 5 postoperative days)	Hours 12, Hours 24, up to 5 after operatives days
surgical re-exploration	Surgical re-exploration for excessive bleeding within 5 postoperative days	Day 0-Day 5,
Sternal closure	Delayed sternal closure	Hours 12
Overall quality of perioperative haemostasis : Use of blood	Perioperative use of blood products and/or plasma derivatives within 2 postoperative days including PRBC, PLT, FFP, fibrinogen concentrate, PCCs, rFVIIa	Day 0-Day 2,
Perioperative biological hemostasis	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	Pre-inclusion - Day 5
Complete blood count	Complete blood count preoperatively, at the end of the surgery, at arrival in ICU and at POD1, 3 and 5.	Pre-inclusion - Day 5
ICU and hospital length of stay	calculated ICU and hospital free days	End of study or early termination- Day 30
Early postoperative morbidity within 30 postoperative days	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	Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
COST-BENEFIT	Hospital incomes will correspond to the Groupe Homogène de Séjour (GHS) of each patient; Hospital expenditure (in-hospital stay, operating room occupancy, transfusions, treatment of infections) valued in the perspective of hospital centers, using data from the national cost studies with common methodology and from analytical accounting.; The difference between hospital incomes and hospital expenditures for each patient will be used to estimate the cost-benefit of the filtration-based autotransfusion SAME device as compared to centrifugation-based autotransfusion devices.	Day 30 /+2 days
Haemoglobin and plasma free haemoglobin	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: haemoglobin level and plasma free haemoglobin will be performed Blood samples will be also collected from the patient just before surgery as well as 6+/-2 hours after surgery to measure plasma free haemoglobin level.	just before surgery as well as 6+/-2 hours after surgery
Hematocrit	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: hematocrit level will be performed.	During the surgery
Complete blood count	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: complete blood count will be performed	During the surgery
Unfractionated heparin anti-Xa	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: unfractionated heparin anti-Xa level will be performed	During the surgery
Fibrinogen	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: fibrinogen level will be performed	During the surgery
Triglycerides	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: triglycerides level will be performed	During the surgery
Total proteins	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: total proteins level will be performed	During the surgery
Potassium	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post treatment) during the first two processing cycles. - Laboratory analyses: potassium level will be performed	During the surgery
Blood viscoelasticity assessment	Patients in whom the salvaged blood from mediastinal shed and residual cardiopulmonary bypass circuit volume will be processed and not reinfused before protamine infusion will be included in this ancillary study. Blood samples will be collected from the patient just before and immediately after re-infusion of the processed blood and sent to the haematology laboratory to perform viscoelasticity assessment Quantra QPlus™	just before and immediately after re-infusion, pré-treatment and just after traitement by the autotransfusion device
Complete bloof count	Patients in whom the salvaged blood from mediastinal shed and residual cardiopulmonary bypass circuit volume will be processed and not reinfused before protamine infusion will be included in this ancillary study. Blood samples will be collected from the patient just before and immediately after re-infusion of the processed blood and sent to the haematology laboratory to complete blood count.	just before and immediately after re-infusion, pré-treatment and just after traitement by the autotransfusion device
INF-γ profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for INF-γ assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
IL-1β-γ profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for IL-1β assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
Il-6 profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for Il-6 assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
IL-8 profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for IL-8 assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
IL-10 profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for IL-10 assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device
TNFα profiling by mass cytometry CyTOF	Blood samples will be collected from the collection reservoir (pre-treatment) of the autotransfusion device and from the reinfusion bag (post-treatment) during the first cycle of processing for immunology assessment (immune profiling by mass cytometry CyTOF). Blood samples will be also collected from the patient for TNFα assessment (by mass cytometry CyTOF) immediately just before surgery as well as one day after surgery	just before surgery, one day after surgery, pré-treatment and just after treatment by the autotransfusion device

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Alexandre Ouattara, MD, PhD, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2024
• Primary Completion (Estimated): February 15, 2026
• Study Completion (Estimated): February 15, 2026

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; bleeding; cardiopulmonary bypass; autotransfusion; perioperative haemostasis; Universal Definition of Perioperative Bleeding; filtration-based autotransfusion; centrifugation-based autotransfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: CHUBX 2022/22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No