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The Cryopreserved vs. Liquid Platelets Trial (CLIP II)

Primary Purpose

Surgical Blood Loss, Hemorrhage

Status

Recruiting

Phase

Phase 3

Locations

Australia

Study Type

Interventional

Intervention

Cryopreserved platelets

Liquid-stored platelets

About this trial

This is an interventional treatment trial for Surgical Blood Loss

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Royal Prince Alfred HospitalRecruiting
The Prince Charles HospitalRecruiting
Townsville HospitalRecruiting
Gold Coast University HospitalRecruiting
St Vincent's Hospital MelbourneRecruiting
Austin HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cryopreserved platelets

Liquid-stored platelets

Arm Description

Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years

Platelets that have been liquid stored, with an expiry of 5 days.

Outcomes

Primary Outcome Measures

Volume of post-surgical bleeding in the first 24 hours

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

Secondary Outcome Measures

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

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)

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

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

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

Full Information

NCT ID

NCT03991481

First Posted

May 9, 2019

Last Updated

November 14, 2022

Sponsor

Australian and New Zealand Intensive Care Research Centre

Collaborators

Australian Red Cross

1. Study Identification

Unique Protocol Identification Number

NCT03991481

Brief Title

The Cryopreserved vs. Liquid Platelets Trial

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 17, 2021 (Actual)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Australian and New Zealand Intensive Care Research Centre

Collaborators

Australian Red Cross

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Surgical Blood Loss, Hemorrhage

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Participants will be allocated to either: cryopreserved or standard liquid-stored platelets

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

808 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cryopreserved platelets

Arm Type

Experimental

Arm Description

Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years

Arm Title

Liquid-stored platelets

Arm Type

Active Comparator

Arm Description

Platelets that have been liquid stored, with an expiry of 5 days.

Intervention Type

Biological

Intervention Name(s)

Cryopreserved platelets

Intervention Description

Platelets that have undergone a process to freeze, store and reconstitute platelets, extending their expiry to 2 years

Intervention Type

Biological

Intervention Name(s)

Liquid-stored platelets

Intervention Description

Liquid-stored platelets as per standard practice

Primary Outcome Measure Information:

Title

Volume of post-surgical bleeding in the first 24 hours

Description

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

Time Frame

First 24 hours from the time of ICU admission

Secondary Outcome Measure Information:

Title

Total volume of post-surgical chest drain bleeding

Description

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

Title

Composite bleeding outcome using the BARC4 criteria

Description

Time Frame

Up to ICU discharge, death or Day 90, whichever occurs first

Title

Number of units of Packed red blood cells transfused

Description

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

Title

Total number of units of Packed red blood cells transfused

Description

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

Title

Occurrence of any one of the following pre-specified potential complications

Description

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

Other Pre-specified Outcome Measures:

Title

Volume of post-surgical chest drain bleeding

Description

Volume of post-surgical chest drain bleeding in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission

Time Frame

in the first 6, 12, 18, 48 hours, beginning from the time of ICU admission

Title

Individual elements of the Bleeding Academic Research Consortium (BARC4) composite bleeding outcome

Description

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)

Time Frame

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

Title

Number of units of blood products

Description

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

Time Frame

in the first 6, 12, 18, 24, 48 hours*, and at ICU discharge or day 90, death or day 90, whichever occurs first

Title

Delay between platelet order and commencement of first study platelet infusion

Description

Delay between platelet order and commencement of first study platelet infusion

Time Frame

Delay between platelet order and commencement of first study platelet infusion, assessed up to 24 hours

Title

Volume of blood in chest drains at the time of ICU admission

Description

Volume of blood in chest drains at the time of ICU admission

Time Frame

From operation commencement up to ICU admission, death or 24 hours, whichever occurs first

Title

Time to commencement of postoperative aspirin and prophylactic heparin

Description

Time to commencement of postoperative aspirin and prophylactic heparin

Time Frame

From ICU admission up to commencement of aspirin and prophylactic heparin, death or day 90, whichever occurs first

Title

Volume of fluid resuscitation recorded on the anaesthetic chart

Description

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

Time Frame

intraoperatively, following ICU admission in the first 6, 12, 18, 24, 48 hours, and at ICU discharge, death or day 90, whichever occurs first

Title

Haemoglobin concentration

Description

Haemoglobin concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Time Frame

results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Title

Platelet count

Description

Platelet count on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Time Frame

results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Title

Fibrinogen concentration

Description

Fibrinogen concentration, on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Time Frame

results measured on day 1 postop and on the last measurement prior to ICU discharge death or day 28, whichever occurs first

Title

INR (International Normalised Ratio)

Description

INR (International Normalised Ratio) on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Time Frame

results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Title

APTT (Activated Partial Thromboplastin Time)

Description

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

Time Frame

results measured on day 1 postop and on the last measurement prior to ICU discharge, death or day 28, whichever occurs first

Title

Incidence of potential complications of DMSO (preservative used in cryopreserved platelets)

Description

Incidence of potential complications of DMSO (preservative used in cryopreserved platelets) such as nausea, headache,tachyacrdia, bradycardia, hypertension

Time Frame

Up to hospital discharge, death or day 90, whichever occurs first

Title

Duration of mechanical ventilation

Description

Duration of mechanical ventilation in the first 90 postoperative days for the index admission

Time Frame

in the first 90 postoperative days for the index admission

Title

Length of postoperative stay in ICU and in hospital

Description

Length of postoperative stay in ICU and in hospital

Time Frame

up to ICU and hospital discharge, death or day 90, whichever occurs first

Title

Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets

Description

Total estimated healthcare cost, incorporating the cost of provision of cryopreserved or liquid-stored platelets

Time Frame

Up to hospital discharge, death or day 90, whichever occurs first

Title

mortality at ICU, hospital and 90 days post-enrolment

Description

mortality at ICU, hospital and 90 days post-enrolment

Time Frame

up to 90 day

Title

ROTEM:EXTEM Clotting time (seconds)

Description

ROTEM: EXTEM Clotting time (seconds)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

ROTEM: EXTEM Clot formation time (seconds)

Description

ROTEM: EXTEM Clot formation time (seconds)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

ROTEM: EXTEM alpha angle (degrees)

Description

ROTEM:EXTEM alpha angle (degrees)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

ROTEM:EXTEM A10 (mm)

Description

ROTEM:EXTEM A10 (mm)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

ROTEM: EXTEM Maximum Clot Firmness (mm)

Description

ROTEM: EXTEM Maximum Clot Firmness (mm)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%)

Description

ROTEM: EXTEM Lysis Index 30 min after CT (LI30) (%)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

TEG: Standard (Kaolin) Reaction (R) time (seconds)

Description

TEG: Standard (Kaolin) Reaction (R) time (seconds)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

TEG: Standard (Kaolin) Clot formation (K) time (seconds)

Description

TEG: Standard (Kaolin) Clot formation (K) time (seconds)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

TEG: Standard (Kaolin) Alpha angle (degrees)

Description

TEG: Standard (Kaolin) Alpha angle (degrees)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

TEG: Standard (Kaolin) Maximum amplitude (mm)

Description

TEG: Standard (Kaolin) Maximum amplitude (mm)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

Title

TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%)

Description

TEG: Standard (Kaolin) Lysis at 30 mins (LY30) (%)

Time Frame

Results before and after last study platelet transfusion (where performed) through study completion up to day 28.

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Belinda D Howe

Phone

+61 3 99030340

belinda.howe@monash.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Reade

Organizational Affiliation

ANZIC-Research Centre; Australian Defence Force, University of Queensland,

Official's Role

Study Chair

Facility Information:

Facility Name

Royal Prince Alfred Hospital

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Gattas

dgattas@gmail.com

First Name & Middle Initial & Last Name & Degree

Heidi Buhr

heidi.buhr@health.nsw.gov.au

Facility Name

The Prince Charles Hospital

City

Brisbane

State/Province

Queensland

ZIP/Postal Code

4032

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bronwyn Pearse

bronwyn.pearse@health.qld.gov.au

First Name & Middle Initial & Last Name & Degree

Donalee O'Brien

donalee.o'brien@health.qld.gov.au

Facility Name

Townsville Hospital

City

Douglas

State/Province

Queensland

ZIP/Postal Code

4814

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anthony Farley

Anthony.Farley@health.qld.gov.au

First Name & Middle Initial & Last Name & Degree

April Win

april.win@jcu.edu.au

Facility Name

Gold Coast University Hospital

City

Southport

State/Province

Queensland

ZIP/Postal Code

4215

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

James McCullough

James.McCullough@health.qld.gov.au

Facility Name

St Vincent's Hospital Melbourne

City

Fitzroy

State/Province

Victoria

ZIP/Postal Code

3065

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ben Slater

ben.slater@svha.org.au

First Name & Middle Initial & Last Name & Degree

Petrea Corcoran

Petrea.CORCORAN@svha.org.au

Facility Name

Austin Hospital

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laurence Weinburg

Laurence.WEINBERG@austin.org.au

First Name & Middle Initial & Last Name & Degree

Glenn Eastwood

Glenn.EASTWOOD@austin.org.au

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

At the completion of the study, at the discretion of the trial Management Committee and Monash University, an extract of the trial data without any patient identifiers may be made available on a case-by-case basis to investigators from reputable research organisations with a defined protocol and analysis plan, using the principles to protect patient anonymity described by the UK Medical Research Council. In accordance with the Australian & New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) Terms of Reference for an endorsed trial, the CTG Chair must approve sharing of data with any third party, manuscripts derived from shared data must be submitted for CTG endorsement prior to publication and must acknowledge the role of the CTG in the original study, and a copy of the published manuscript must be provided to the CTG office.

IPD Sharing Time Frame

De-identified data availability will begin 9 months after publication of the individual patient data meta-analysis combining both trial results, and end 36 months after this publication.

IPD Sharing Access Criteria

Submissions to use data with investigators from reputable research organisations with a defined protocol and analysis plan, using the principles to protect patient anonymity described by the UK Medical Research Council.

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The Cryopreserved vs. Liquid Platelets Trial

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