The Cryopreserved vs. Liquid Platelets Trial

Hemorrhage Clinical Trial

— CLIP II  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03991481
• Other study ID #: ANZIC-RC/MR002
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 17, 2021
• Est. completion date: August 2024

Study information

• Verified date: April 2024
• Source: Australian and New Zealand Intensive Care Research Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 388
• Est. completion date: August 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Loss, Surgical
• Hemorrhage
• Surgical Blood Loss

Intervention

Biological:
• Cryopreserved platelets
Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years
• Liquid-stored platelets
Liquid-stored platelets as per standard practice

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	Townsville Hospital	Douglas	Queensland
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Australian and New Zealand Intensive Care Research Centre	Australian Red Cross

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Volume of post-surgical chest drain bleeding	Volume of post-surgical chest drain bleeding in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission	in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission
Other	Individual elements of the Bleeding Academic Research Consortium (BARC4) composite bleeding outcome	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)	Up to ICU discharge, death or day 90, whichever occurs first
Other	Number of units of blood products	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	in the first 6, 12, 18, 24, 48 hours*, and at ICU discharge or day 90, death or day 90, whichever occurs first
Other	Delay between platelet order and commencement of first study platelet infusion	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
Other	Volume of blood in chest drains at the time of ICU admission	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
Other	Time to commencement of postoperative aspirin and prophylactic heparin	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
Other	Volume of fluid resuscitation recorded on the anaesthetic chart	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	intraoperatively, following ICU admission in the first 6, 12, 18, 24, 48 hours, and at ICU discharge, death or day 90, whichever occurs first
Other	Haemoglobin concentration	Haemoglobin concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first	results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
Other	Platelet count	Platelet count on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first	results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
Other	Fibrinogen concentration	Fibrinogen concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first	results measured on day 1 postop and on the last measurement prior to ICU discharge death or day 28, whichever occurs first
Other	INR (International Normalised Ratio)	INR (International Normalised Ratio) on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first	results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
Other	APTT (Activated Partial Thromboplastin Time)	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	results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first
Other	Incidence of potential complications of DMSO (preservative used in cryopreserved platelets)	Incidence of potential complications of DMSO (preservative used in cryopreserved platelets) such as nausea, headache,tachyacrdia, bradycardia, hypertension	Up to hospital discharge, death or day 90, whichever occurs first
Other	Duration of mechanical ventilation	Duration of mechanical ventilation in the first 90 postoperative days for the index admission	in the first 90 postoperative days for the index admission
Other	Length of postoperative stay in ICU and in hospital	Length of postoperative stay in ICU and in hospital	up to ICU and hospital discharge, death or day 90, whichever occurs first
Other	Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets	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
Other	mortality at ICU, hospital and 90 days post-enrolment	mortality at ICU, hospital and 90 days post-enrolment	up to 90 day
Other	ROTEM:EXTEM Clotting time (seconds)	ROTEM: EXTEM Clotting time (seconds)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	ROTEM: EXTEM Clot formation 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.
Other	ROTEM: EXTEM alpha angle (degrees)	ROTEM:EXTEM alpha angle (degrees)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	ROTEM:EXTEM A10 (mm)	ROTEM:EXTEM A10 (mm)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	ROTEM: EXTEM Maximum Clot Firmness (mm)	ROTEM: EXTEM Maximum Clot Firmness (mm)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%)	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.
Other	TEG: Standard (Kaolin) Reaction (R) time (seconds)	TEG: Standard (Kaolin) Reaction (R) time (seconds)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	TEG: Standard (Kaolin) Clot formation (K) 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.
Other	TEG: Standard (Kaolin) Alpha angle (degrees)	TEG: Standard (Kaolin) Alpha angle (degrees)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	TEG: Standard (Kaolin) Maximum amplitude (mm)	TEG: Standard (Kaolin) Maximum amplitude (mm)	Results before and after last study platelet transfusion (where performed) through study completion up to day 28.
Other	TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%)	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.
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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