The Cryopreserved vs. Liquid Platelets Trial

Study Overview
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Brief Summary
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This trial is a phase III multicentre blinded randomised controlled clinical non-inferiority trial of cryopreserved platelets vs. conventional liquid-stored platelets for the management of surgical bleeding. The aim of the study is to assess the efficacy, safety and cost effectiveness of cryopreserved platelets, compared to conventional liquid-stored platelets, for the management of surgical bleeding. This trial will recruit cardiac surgical patients deemed to be at high risk of surgical bleeding and who may potentially require transfusion of platelets. It is estimated to require 808 high-risk cardiac surgical patients to be recruited, to obtain 202 patients who receive transfused study platelets for surgical bleeding.

Detailed Description
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For logistic reasons and in order to use this scarce resource optimally, liquid-stored platelets are not stored in smaller hospitals, or in deployed military hospitals. Patients in these hospitals therefore currently have limited or no access to platelet transfusion. Cryopreservation of platelets is a promising technology that would allow smaller hospitals to provide platelet transfusions, reduce overall platelet wastage, and possibly produce better patient outcomes through more effective haemostasis. This is a phase III multicentre blinded randomised controlled clinical non-inferiority trial of cryopreserved platelets vs. conventional liquid-stored platelets for the management of surgical bleeding. The aim of the study is to assess the efficacy, safety and cost effectiveness of cryopreserved platelets, compared to conventional liquid-stored platelets, for the management of surgical bleeding. This trial will recruit cardiac surgical patients deemed to be at high risk of surgical bleeding and who may potentially require transfusion of platelets. It is estimated to require 808 high-risk cardiac surgical patients to be recruited, to obtain 202 patients who receive transfused study platelets for surgical bleeding. The study will recruit patients in Australian tertiary hospitals.The study hypothesis is that cryopreserved platelets will be at least as effective as conventional liquid-stored platelets in the treatment of active bleeding due to surgery.

Official Title
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A Phase III Multicentre Blinded Randomised Controlled Clinical Non-inferiority Trial of Cryopreserved Platelets vs. Conventional Liquid-stored Platelets for the Management of Surgical Bleeding

Conditions
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Surgical Blood Loss, Hemorrhage

Intervention / Treatment
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* Biological: Cryopreserved platelets
* Biological: Liquid-stored platelets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiac surgery patients identified preoperatively as having a high risk of platelet transfusion by either: the ACSePT (Australian Cardiac Surgery Platelet Transfusion (score)) risk prediction tool score ≥1 OR the judgement of the clinicians caring for the patient Written informed consent obtained prior to surgery Exclusion Criteria: Aged less than 18 years Females of child-bearing age (18- 55 years) who are RhD (Rhesus type D)-negative or whose RhD (Rhesus type D) status is unknown Receipt of platelet transfusion during this hospital admission Deep Vein Thrombosis or Pulmonary Emboli first diagnosed within the preceding 6 months More than one lifetime episode of Deep Vein Thrombosis or Pulmonary Emboli Known inherited or acquired bleeding disorder (e.g. haemophilia, von Willebrand Disease, idiopathic thrombocytopenic purpura, aplastic anaemia, haematological malignancy, chronic liver disease), or any undiagnosed bleeding condition, if (and only if) such a disorder or condition is associated with a significant laboratory abnormality at the time of preoperative screening. i.e. preoperative platelet count <50 000 or INR (International Normalised Ratio) >2 or aPTT (Activated Partial Thromboplastin Time) > 2 x upper limit of normal. Treatment with warfarin, IV heparin or low-molecular weight heparin at full therapeutic anticoagulant doses, or other anticoagulant or anti-platelet medications such as factor Xa inhibitors (rivaroxaban, apixaban); factor II inhibitors (dabigatran); adenosine diphosphate receptor inhibitors (clopidogrel, prasugrel, ticagrelor, ticlopidine); glycoprotein IIB/IIIA inhibitors (abciximab, eptifibatide, tirofiban); phosphodiesterase inhibitors (cilostazol); or adenosine reuptake inhibitors (dipyridamole) UNLESS this medication has been discontinued in advance of surgery and its effect allowed to dissipate. Known allergy to dimethylsulphoxide (DMSO) Planned presence of an arterial line and central venous catheter for less than 12 hours postoperatively. Known objection to receipt of human blood components The treating physician believes it is not in the best interest of the patient to be randomised in this trial Previous enrolment during this admission in a clinical trial of a medication or technique thought to influence bleeding, with the exception of any trial of aspirin (i.e. trials involving aspirin are permitted), OR previous enrolment in a clinical trial with a protocol that affects the transfusion of blood products. Previous enrolment in this study
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
Interventional Model Description: Participants will be allocated to either: cryopreserved or standard liquid-stored platelets
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryopreserved platelets<br>Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years | Biological: Cryopreserved platelets<br>* Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years<br>|
| Active Comparator: Liquid-stored platelets<br>Platelets that have been liquid stored, with an expiry of 5 days. | Biological: Liquid-stored platelets<br>* Liquid-stored platelets as per standard practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of post-surgical bleeding in the first 24 hours | Volume of post-surgical bleeding in the chest drains after cardiac surgery | First 24 hours from the time of ICU admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total volume of post-surgical chest drain bleeding | Total volume of post-surgical chest drain bleeding, beginning from the time of ICU admission until drain removal | From ICU admission up to removal of drains, death or day 28, whichever occurs first | 
| Composite bleeding outcome using the BARC4 criteria | Composite bleeding outcome using the Bleeding Academic Research Consortium (BARC4) criteria (intracranial bleeding within 48 hours; reoperation after closure of sternotomy; transfusion of ≥5 Units whole blood or RBCs (red blood cells) within the 48 hour intra- or post-operative period (excluding cell saver blood); chest tube output ≥2 Litres within a 24 hour period) | Up to ICU discharge, death or Day 90, whichever occurs first | 
| Number of units of Packed red blood cells transfused | Number of units of Packed red blood cells transfused in the first 24 hours after admission to ICU | in the first 24 hours after admission to ICU | 
| Total number of units of Packed red blood cells transfused | Total number of units of Packed red blood cells transfused by the time of ICU discharge, including intraoperative transfusion | From operation commencement up to ICU discharge, death or day 90, whichever occurs first | 
| Occurrence of any one of the following pre-specified potential complications | Occurrence of any one of the following specified potential complications: venous thromboembolism arterial occlusion acute coronary syndrome acute respiratory distress syndrome | Up to ICU discharge, death or day 90, whichever occurs first |