Clinical trial NCT03991481: The Cryopreserved vs. Liquid Platelets Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Surgical Blood Loss
Hemorrhage
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: Australian Red Cross
First posted: 2019-06-19
Enrollment: 388
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be allocated to either: cryopreserved or standard liquid-stored platelets
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Volume of post-surgical bleeding in the first 24 hours
timeFrame: First 24 hours from the time of ICU admission
Secondary outcomes:
measure: Total volume of post-surgical chest drain bleeding
timeFrame: From ICU admission up to removal of drains, death or day 28, whichever occurs first
measure: Composite bleeding outcome using the BARC4 criteria
timeFrame: Up to ICU discharge, death or Day 90, whichever occurs first
measure: Number of units of Packed red blood cells transfused
timeFrame: in the first 24 hours after admission to ICU
measure: Total number of units of Packed red blood cells transfused
timeFrame: From operation commencement up to ICU discharge, death or day 90, whichever occurs first
measure: Occurrence of any one of the following pre-specified potential complications
timeFrame: Up to ICU discharge, death or day 90, whichever occurs first
Other outcomes:
measure: Volume of post-surgical chest drain bleeding
timeFrame: in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission
measure: Individual elements of the Bleeding Academic Research Consortium (BARC4) composite bleeding outcome
timeFrame: Up to ICU discharge, death or day 90, whichever occurs first
measure: Number of units of blood products
timeFrame: in the first 6, 12, 18, 24, 48 hours*, and at ICU discharge or day 90, death or day 90, whichever occurs first
measure: Delay between platelet order and commencement of first study platelet infusion
timeFrame: Delay between platelet order and commencement of first study platelet infusion, assessed up to 24 hours
measure: Volume of blood in chest drains at the time of ICU admission
timeFrame: From operation commencement up to ICU admission, death or 24 hours, whichever occurs first
measure: Time to commencement of postoperative aspirin and prophylactic heparin
timeFrame: From ICU admission up to commencement of aspirin and prophylactic heparin, death or day 90, whichever occurs first
measure: Volume of fluid resuscitation recorded on the anaesthetic chart
timeFrame: intraoperatively, following ICU admission in the first 6, 12, 18, 24, 48 hours, and at ICU discharge, death or day 90, whichever occurs first
measure: Haemoglobin concentration
timeFrame: results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
measure: Platelet count
timeFrame: results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
measure: Fibrinogen concentration
timeFrame: results measured on day 1 postop and on the last measurement prior to ICU discharge death or day 28, whichever occurs first
measure: INR (International Normalised Ratio)
timeFrame: results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
measure: APTT (Activated Partial Thromboplastin Time)
timeFrame: results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
measure: Incidence of potential complications of DMSO (preservative used in cryopreserved platelets)
timeFrame: Up to hospital discharge, death or day 90, whichever occurs first
measure: Duration of mechanical ventilation
timeFrame: in the first 90 postoperative days for the index admission
measure: Length of postoperative stay in ICU and in hospital
timeFrame: up to ICU and hospital discharge, death or day 90, whichever occurs first
measure: Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets
timeFrame: Up to hospital discharge, death or day 90, whichever occurs first
measure: mortality at ICU, hospital and 90 days post-enrolment
timeFrame: up to 90 day
measure: ROTEM:EXTEM Clotting time (seconds)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: ROTEM: EXTEM Clot formation time (seconds)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: ROTEM: EXTEM alpha angle (degrees)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: ROTEM:EXTEM A10 (mm)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: ROTEM: EXTEM Maximum Clot Firmness (mm)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: TEG: Standard (Kaolin) Reaction (R) time (seconds)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: TEG: Standard (Kaolin) Clot formation (K) time (seconds)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: TEG: Standard (Kaolin) Alpha angle (degrees)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: TEG: Standard (Kaolin) Maximum amplitude (mm)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
measure: TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%)
timeFrame: Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Locations:
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Douglas
country: Australia
facility: Townsville Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
Study officials:
affiliation: ANZIC-Research Centre; Australian Defence Force, University of Queensland,
name: Michael Reade
role: STUDY_CHAIR
References: