Transfusion of Cold-stored Platelet Concentrates

Study Overview
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Brief Summary
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This study will investigate the effects of Leukocyte reduced cold-stored platelet transfusions used in treatment of immediate postoperative blood loss in patients undergoing thoracic surgery in combination with extracorporal circulation. Today platelet concentrates are stored at 22 degrees C . This is a prospective, randomized, unblinded, non-inferiority two-arm study. Aim of study is to compare platelet function in bleeding patients transfused with leukoreduced platelet concentrates stored cold (4 degrees C) and in room temperature (22 degrees C). Storage time for RCT platelet concentrates are up to 7 days. Patients with expected time on extracorporal circulation more than 120 minutes and/or medical platelet inhibitors will be included. Platelet function will be assessed by use of Multiplate Aggregometry, Thromboelastography (TEG) and/or Thromboelastometry (ROTEM). In addition post operative bleeding, and adverse events will be recorded. After completion of recruitment of patients to RCT study of platelet stored cold for up to 7 days, a follow up prospective observational study of platelets stored cold for up to 14 days is performed. Additonal information 2019, May 03: This trial was registered on Clinical Trials.gov with an original plan to use non-inferiority testing of between-group differences in platelet function. Due to lack of evidence needed to set acceptable tolerance margins for the non-inferiority testing, independent reviewers with expertise in clinical trial design recommended they be replaced by standard tests of superiority, commensurate with the early phase of the trial. Further, post-operative chest tube drainage was chosen as the primary outcome to better present the pilot study's focus on the control of clinically significant bleeding.

Detailed Description
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This is a prospective, randomized, unblinded, non-inferiority two-arm study were Arm 1 patients will receive Leukocyte reduced cold-stored platelet concentrates and Arm 2 patients will receive leukoreduced room-temperature-stored (22 degrees C) platelet concentrates. Patients with expected time on extracorporal circulation more than 120 minutes and/or medical platelet inhibitors will be included. The number of patients included is set to 20 patients in each arm, as there is not sufficient information available in the literature to conduct power calculations. The hypothesis is that cold stored platelets are not inferior to room temperature platelet concentrates. Baseline patient data and information on intervention and post operative recovery will be collected from the Medical journals together with information on transfusion episodes and Blood Components. Blood samples will be retrieved from study participants at specific intervals: baseline, immediately after surgery, at arrival at ICU, before and after (every) platelet transfusion episode, 24 hours post operation, and if indicated, during hospital stay. Blood samples will be investigated for platelet function, coagulation parameters, hematologic parameters, and other risk factors for adverse events. If transfusion reactions occur, additional test of patient and the Blood Component(s) transfused will be performed. Samples will be collected and stored in the biobank for cytokines, complement and allergy analysis. After completion of recruitment of patients to RCT study of platelet concentrates stored cold for up to 7 days, a follow up prospective observational study of platelets stored cold for up to 14 days is performed. Additonal information 2019, May 03: This trial was registered on Clinical Trials.gov with an original plan to use non-inferiority testing of between-group differences in platelet function. Due to lack of evidence needed to set acceptable tolerance margins for the non-inferiority testing, independent reviewers with expertise in clinical trial design recommended they be replaced by standard tests of superiority, commensurate with the early phase of the trial. Further, post-operative chest tube drainage was chosen as the primary outcome to better present the pilot study's focus on the control of clinically significant bleeding.

Official Title
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Transfusion Therapy in Patients Undergoing Cardiac Surgery in Combination With Late Withdrawal of Drug Induced Platelet Inhibition or Prolonged Extra-corporal Circulation Time

Conditions
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Cardiovascular Disease Other, Bleeding, Surgery

Intervention / Treatment
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* Other: Cold stored platelets
* Other: Room temperature platelets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing urgent/semiurgent thoracic surgery Expected long extracorporal time (>120 minutes) and/or use of dual platelet inhibition drugs Patients likely to require platelet transfusion Patients capable of providing informed consent Exclusion Criteria: Patients who will not provide informed consent Patients with congenital coagulopathies or hemostatic disorders (von willebrands disease, hemophilia etc)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cold stored platelets<br>Intervention: Leukoreduced platelet concentrates stored at 4 degrees C for treatment of bleeding after Cardiac surgery | Other: Cold stored platelets<br>* Intervention: Leukoreduced platelet concentrates stored at 4 degrees C for treatment of bleeding after Cardiac surgery. Storage time for RCT platelet concentrates are up to 7 days.<br>* Other names: Trombocytes, Platelet concentrates;|
| Active Comparator: Room temperature platelets<br>Intervention: Leukoreduced platelet concentrates stored at 22 degrees C for treatment of bleeding after Cardiac surgery | Other: Room temperature platelets<br>* Intervention: Leukoreduced platelet concentrates stored at 22 degrees C for treatment of bleeding after Cardiac surgery. Storage time for RCT platelet concentrates are up to 7 days.<br>* Other names: Trombocytes, Platelet concentrates;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chest drain output (postoperative bleeding) | Information retrieved from Medical Journal | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of altered platelet function confirmed by Point-of-Care measurements | Evaluate in vitro changes in platelet function by use of the following Point-of-Care measurements; Multiplate whole blood impedance aggregometry, Thromboelastography, and ROTEM | Up to 24 hours after surgery | 
| Number of Blood Products transfused as a Measure of Bleeding | Information retrieved from Medical Journal | From date of inclusion during hospital stay, up to 4 weeks | 
| Number of Participants with thromboembolic events as a Measure of Safety | Information retrieved from Medical Journal | From date of procedure until the date of first documented event during hospital stay, up to 4 weeks | 
| Number of Participants with other adverse events as a Measure of Safety | Information retrieved from Medical Journal | From date of procedure until the date of first documented event during hospital stay, up to 4 weeks | 
| Number of Participants with transfusion complication as a Measure of Safety | Information retrieved from Medical Journal | From date of procedure until the date of first documented event during hospital stay, up to 4 weeks | 
| Hemoglobin value | Information retrieved from Medical Journal | From date of inclusion, daily during hospital stay, up to 4 weeks | 
| Hematocrit | Information retrieved from Medical Journal | Up to 24 hours after surgery | 
| Leukocyte count | Information retrieved from Medical Journal | Up to 24 hours after surgery | 
| Platelet count | Information retrieved from Medical Journal | From date of inclusion, daily during hospital stay, up to 4 weeks | 
| Fibrinogen | Information retrieved from Medical Journal | Up to 24 hours after surgery | 
| International normalized ratio (INR) | Information retrieved from Medical Journal | Up to 24 hours after surgery | 
| Activated Partial Thromboplastin time (APTT) | Information retrieved from Medical Journal | Baseline, up to 24 hours and at the date of first documented thromboembolic event during hospital stay, up to 4 weeks | 
| Allergy analysis as a Measure of Risk of transfusion complication | Information retrieved from Medical Journal | Baseline,and the date of first documented event during hospital stay, up to 4 weeks | 
| Complement analysis as a Measure of risk of transfusion complication | Information retrieved from Medical Journal | Baseline,and the date of first documented event during hospital stay, up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bleeding, Cardiac surgery, platelet transfusion