The Cryopreserved vs. Liquid Platelets Trial

Phase 3Active Not RecruitingNCT03991481

Australian and New Zealand Intensive Care Research Centre388 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. Written informed consent obtained prior to surgery Exclusion Criteria: 1. Aged less than 18 years 2. Females of child-bearing age (18- 55 years) who are RhD (Rhesus type D)-negative or whose RhD (Rhesus type D) status is unknown 3. Receipt of platelet transfusion during this hospital admission 4. Deep Vein Thrombosis or Pulmonary Emboli first diagnosed within the preceding 6 months 5. More than one lifetime episode of Deep Vein Thrombosis or Pulmonary Emboli 6. 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. 7. 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. 8. Known allergy to dimethylsulphoxide (DMSO) 9. Planned presence of an arterial line and central venous catheter for less than 12 hours postoperatively. 10. Known objection to receipt of human blood components 11. The treating physician believes it is not in the best interest of the patient to be randomised in this trial 12. 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. 13. Previous enrolment in this study

Locations (6)

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

The Prince Charles Hospital

Brisbane, Queensland, Australia

Townsville Hospital

Douglas, Queensland, Australia

Gold Coast University Hospital

Southport, Queensland, Australia

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Outcomes

Primary Outcomes

Volume of post-surgical bleeding in the first 24 hours

Volume of post-surgical bleeding in the chest drains after cardiac surgery

Time frame: First 24 hours from the time of ICU admission

Secondary Outcomes

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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Up to ICU discharge, death or day 90, whichever occurs first