Cold Stored Whole Blood in Cardiothoracic Surgery

Cold Stored Whole Blood in Treatment of Bleeding in Patients Undergoing Cardiothoracic Surgery

In vitro platelet function and post-transfusion platelet recovery of platelets stored in whole blood decline during storage. In this pilot randomized clinical trial we aim to investigate the impact of storage time of whole blood on the effect and safety in treatment of immediate blood loss in patients undergoing complex cardiothoracic surgery. The study is designed as an exploratory superiority study to support feasibility and provide critical guidance for future, more definitive randomized trials. In the study the test group will receive CPD whole blood leukocyte-depleted with a platelet-sparing filter and stored for 15-21 days whereas the control group patients will receive leukocyte-depleted CPD whole blood stored for less than 7 days.

Study Overview

• Status: Recruiting
• Conditions: Bleeding
• Intervention / Treatment: Other: Whole Blood transfusion

Detailed Description

A challenge for implementation of Whole Blood programs in civilian health services has been an uncertainty regarding the impact of storage on the clinical effect of the whole blood transfusion, especially when it comes to platelet function which is essential to hemostasis. In vitro platelet function and post-transfusion platelet recovery decline with increasing storage time of the whole blood.

In this pilot randomized clinical trial we aim to investigate the impact of storage time of whole blood on the effect and safety in treatment of immediate blood loss in patients undergoing complex cardiothoracic surgery. The study is designed as an exploratory superiority study to support feasibility and provide critical guidance for future, more definitive randomized trials. In the study the test group will receive CPD whole blood leukocyte-depleted with a platelet-sparing filter and stored for 15-21 days whereas the control group patients will receive leukocyte-depleted CPD whole blood stored for less than 7 days. A control group receiving standard care (blood component-based transfusion) may be included.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Torunn O Apelseth, PhD; Phone Number: +4755972470; Email: torunn.oveland.apelseth@helse-bergen.no
• Study Contact Backup: Name: Kristin G Hagen, MD; Phone Number: +4755972470; Email: kristin.gjerde.hagen@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway
    • Recruiting
    • Haukeland University Hospital
    • Contact: Torunn O Apelseth, PhD; Phone Number: +4755972470; Email: torunn.oveland.apelseth@helse-bergen.no
    • Contact: Kristin G Hagen, MD; Phone Number: +55972470; Email: kristin.gjerde.hagen@helse-bergen.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients undergoing cardiothoracic, cardiac, or aortic surgery
2. Patients with complex surgical procedures and expected cardiopulmonary bypass (CPB) time over 120 minutes
3. Patients capable of providing informed consent to participate in the study

Exclusion Criteria:

1. Patients not capable of providing informed consent to participate or who will not provide informed consent
2. Patients with known congenital coagulopathies or hemostatic disorders (von Willebrands Disease, hemophilia etc)
3. Patients with known erythrocyte- or platelet/HLA antibodies
4. Patients with a particular increased surgical risk with expected need of ECMO
5. Patients with preoperative EuroScore II ≥ 30

5. RhD negative patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole Blood stored for 15-21 days; CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for 15-21 days	Other: Whole Blood transfusion; In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.
Active Comparator: Whole Blood stored for less than 7 days; CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for less than 7 days. We aim at using as fresh as possible.	Other: Whole Blood transfusion; In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.
Active Comparator: Whole Blood stored for 8-14 days; CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for 8-14 days. This group may be added if deemed of interest after interim analysis.	Other: Whole Blood transfusion; In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.
Active Comparator: Standard Blood Component; This group may be added for comparison if deemed of interest after interim analysis.	Other: Whole Blood transfusion; In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss	Comparison of postoperative immediate blood loss (measured by chest drain output and/or bleeding score) in patients receiving fresher or older cold stored whole blood.	24 hours (8:00 am morning after surgery)
Blood usage	Comparison of amount of whole blood and blood components given	24 hours (8:00 am morning after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	Length of stay	30 days
Mortality	Mortality	30 days
INR	Coagulation measured as INR	24 hours (8:00 am morning after surgery)
APTT	Coagulation measured as APTT	24 hours (8:00 am morning after surgery)
Thromboelastography	Thromboelastography (TEG6s)	24 hours (8:00 am morning after surgery)
Platelet aggregometry	Platelet aggregation measured by Multiplate impedance aggregometry (Mulitplate analyzer)	24 hours (8:00 am morning after surgery)
Platelet count	Platelet count	24 hours (8:00 am morning after surgery)
Hemoglobin concentration	Hemoglobin concentration	24 hours (8:00 am morning after surgery)
Erythrocyte count	Erythrocyte count	24 hours (8:00 am morning after surgery)
Hematocrit	Hematocrit or erytrocyte volume fraction, i.e.the volume percentage (vol%) of red blood cells (RBC) in blood,	24 hours (8:00 am morning after surgery)
Fibrinogen concentration	Fibrinogen concentration	24 hours (8:00 am morning after surgery)
Metabolomic profile	Investigation of blood cell metabolism and metabolic profile by use of high resolution mass spectometry	24 hours (8:00 am morning after surgery)
White blood cell count	White blood cell count	24 hours (8:00 am morning after surgery)
Bilirubin	Hemolysis measured as Bilirubin	Up to 7 days
Haptoglobin	Hemolysis measured as Haptoglobin	Up to 7 days
Lactate dehydrogenase	Lactate dehydrogenase (LD)	Up to 7 days
Direct antiglobin test	Direct antiglobin test (DAT)	Up to 7 days
Anti-A antibodies	Anti-A antibodies	Up to 7 days
Anti-B antibodies	Anti-B antibodies	Up to 7 days
Hemostatic agents	Use of hemostatic agents (coagulation factor concentrates, fibriongen concentrate)	24 hours (8:00 am morning after surgery)
Other medications	Use of other medications potentially affecting bleeding (including tranexamacid, calcium etc.)	24 hours (8:00 am morning after surgery)
Adverse events	Adverse events	30 days

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Study Chair: Einar K Kristoffersen, PhD, Helse Bergen

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2021
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: 2019/01294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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