Hemorrhage, Surgical Blood Loss
Conditions
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.
Interventions
BIOLOGICALLiquid-stored platelets
Liquid-stored platelets as per standard practice
BIOLOGICALCryopreserved platelets
Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years
Sponsors
Australian Red Cross
Australian and New Zealand Intensive Care Research Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Platelets will be allocated to participant by unblinded blood bank staff. The platelets will be supplied by the blood bank with an opaque cover that obscures their method of storage (cryopreserved or liquid-stored), but that retain the original Blood Service information for checking.
Intervention model description
Participants will be allocated to either: cryopreserved or standard liquid-stored platelets
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume of post-surgical bleeding in the first 24 hours | First 24 hours from the time of ICU admission | Volume of post-surgical bleeding in the chest drains after cardiac surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total volume of post-surgical chest drain bleeding | From ICU admission up to removal of drains, death or day 28, whichever occurs first | Total volume of post-surgical chest drain bleeding, beginning from the time of ICU admission until drain removal |
| Composite bleeding outcome using the BARC4 criteria | Up to ICU discharge, death or Day 90, whichever occurs first | 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) |
| Number of units of Packed red blood cells transfused | in the first 24 hours after admission to ICU | Number of units of Packed red blood cells transfused in the first 24 hours after admission to ICU |
| Total number of units of Packed red blood cells transfused | From operation commencement up to ICU discharge, death or day 90, whichever occurs first | Total number of units of Packed red blood cells transfused by the time of ICU discharge, including intraoperative transfusion |
| Occurrence of any one of the following pre-specified potential complications | Up to ICU discharge, death or day 90, whichever occurs first | Occurrence of any one of the following specified potential complications: venous thromboembolism arterial occlusion acute coronary syndrome acute respiratory distress syndrome |
Other
| Measure | Time frame | Description |
|---|---|---|
| Volume of blood in chest drains at the time of ICU admission | From operation commencement up to ICU admission, death or 24 hours, whichever occurs first | Volume of blood in chest drains at the time of ICU admission |
| Time to commencement of postoperative aspirin and prophylactic heparin | From ICU admission up to commencement of aspirin and prophylactic heparin, death or day 90, whichever occurs first | Time to commencement of postoperative aspirin and prophylactic heparin |
| Volume of fluid resuscitation recorded on the anaesthetic chart | intraoperatively, following ICU admission in the first 6, 12, 18, 24, 48 hours, and at ICU discharge, death or day 90, whichever occurs first | Volume of fluid resuscitation recorded on the anaesthetic chart intraoperatively, following ICU admission in the first 6, 12, 18, 24, 48 hours, and at ICU discharge |
| Haemoglobin concentration | results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first | Haemoglobin concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first |
| Platelet count | results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first | Platelet count on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first |
| Fibrinogen concentration | results measured on day 1 postop and on the last measurement prior to ICU discharge death or day 28, whichever occurs first | Fibrinogen concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first |
| INR (International Normalised Ratio) | results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first | INR (International Normalised Ratio) on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first |
| APTT (Activated Partial Thromboplastin Time) | results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first | APTT (Activated Partial Thromboplastin Time) on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first |
| Incidence of potential complications of DMSO (preservative used in cryopreserved platelets) | Up to hospital discharge, death or day 90, whichever occurs first | Incidence of potential complications of DMSO (preservative used in cryopreserved platelets) such as nausea, headache,tachyacrdia, bradycardia, hypertension |
| Duration of mechanical ventilation | in the first 90 postoperative days for the index admission | Duration of mechanical ventilation in the first 90 postoperative days for the index admission |
| Length of postoperative stay in ICU and in hospital | up to ICU and hospital discharge, death or day 90, whichever occurs first | Length of postoperative stay in ICU and in hospital |
| TEG: Standard (Kaolin) Alpha angle (degrees) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | TEG: Standard (Kaolin) Alpha angle (degrees) |
| mortality at ICU, hospital and 90 days post-enrolment | up to 90 day | mortality at ICU, hospital and 90 days post-enrolment |
| ROTEM:EXTEM Clotting time (seconds) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM: EXTEM Clotting time (seconds) |
| ROTEM: EXTEM Clot formation time (seconds) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM: EXTEM Clot formation time (seconds) |
| ROTEM: EXTEM alpha angle (degrees) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM:EXTEM alpha angle (degrees) |
| ROTEM:EXTEM A10 (mm) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM:EXTEM A10 (mm) |
| ROTEM: EXTEM Maximum Clot Firmness (mm) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM: EXTEM Maximum Clot Firmness (mm) |
| ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%) |
| TEG: Standard (Kaolin) Reaction (R) time (seconds) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | TEG: Standard (Kaolin) Reaction (R) time (seconds) |
| TEG: Standard (Kaolin) Clot formation (K) time (seconds) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | TEG: Standard (Kaolin) Clot formation (K) time (seconds) |
| TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%) |
| Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets | Up to hospital discharge, death or day 90, whichever occurs first | Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets |
| Volume of post-surgical chest drain bleeding | in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission | Volume of post-surgical chest drain bleeding in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission |
| Individual elements of the Bleeding Academic Research Consortium (BARC4) composite bleeding outcome | Up to ICU discharge, death or day 90, whichever occurs first | Individual elements of the Bleeding Academic Research Consortium (BARC4) composite bleeding outcome (intracranial bleeding within 48 hours; reoperation after closure of sternotomy; transfusion of ≥5 Units whole blood or RBC (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) |
| Number of units of blood products | in the first 6, 12, 18, 24, 48 hours*, and at ICU discharge or day 90, death or day 90, whichever occurs first | Number of units of blood products (Packed red blood cells, plasma, cryoprecipitate, open-label platelets, fibrinogen concentrate, recombinant factor VIIa, prothrombin complex concentrate, whole blood) transfused intraoperatively, in the first 6, 12, 18, 24, 48 hours, and at ICU discharge |
| Delay between platelet order and commencement of first study platelet infusion | Delay between platelet order and commencement of first study platelet infusion, assessed up to 24 hours | Delay between platelet order and commencement of first study platelet infusion |
| TEG: Standard (Kaolin) Maximum amplitude (mm) | Results before and after last study platelet transfusion (where performed) through study completion up to day 28. | TEG: Standard (Kaolin) Maximum amplitude (mm) |
Countries
Australia
Outcome results
None listed