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Trial registered on ANZCTR


Registration number
ACTRN12621000271808
Ethics application status
Approved
Date submitted
14/01/2021
Date registered
11/03/2021
Date last updated
14/01/2024
Date data sharing statement initially provided
11/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Cryopreserved vs Liquid Platelets (CLiPNZ-II) for the management of post operative bleeding in patients undergoing cardiac surgery
Scientific title
Phase III, multicentre, blinded, randomised controlled trial of cryopreserved platelets vs conventional liquid-stored platelets for the management of post-operative bleeding in patients undergoing cardiac surgery
Secondary ID [1] 302960 0
none
Universal Trial Number (UTN)
U1111-1262-3922
Trial acronym
CLiPNZ-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bleeding 319995 0
Cardiac Surgery 320631 0
Condition category
Condition code
Blood 317926 317926 0 0
Other blood disorders
Surgery 318487 318487 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cryopreserved (CPS) platelets (intervention arm): Cryopreserved group O (low antibody titre – i.e. universal donor) platelets will be prepared NZ Blood Service staff using the approved methodology in the hospital blood bank
The treating clinician and clinical staff are blinded to the study group allocation. Transfusion indication, timing and number of platelets will be determined by treating clinicians.
Platelet transfusion will begin in either the operating theatre or ICU (but must occur within 24hrs of ICU admission). When a clinical decision is made to transfuse platelets, the ordering clinician will request platelets from the blood bank according to usual local hospital policy.
New Zealand Blood Service has developed a novel method of manufacturing cryopreserved platelets, this method doesn't require any washing of platelets and the thawing and reconstitution in plasma is simplified by the use of a two-chamber bag. Cryopreservation of platelets increases the shelf life to 2 years by keeping the platelets frozen at -80C
Intervention code [1] 319246 0
Treatment: Other
Comparator / control treatment
Conventional liquid-stored (RTS) platelets (usual care arm): Patients will receive conventional liquid-stored pooled buffy coat platelets or apheresis platelets. Participants will be identified and enrolled by the research staff at each participating hospital using a secure we-based system. Participants will receive the next available platelets in the blood bank.
Control group
Active

Outcomes
Primary outcome [1] 325932 0
Volume of chest-tube bleeding in the first 24 hours by using the drainage volume recorded in the medical notes by nursing staff
Timepoint [1] 325932 0
First 24 hours - will be measured from the time of admission to ICU
Secondary outcome [1] 389588 0
• Volume of post-surgical bleeding in the first 6, 12, 18, 48 hours, and total recorded in the medical notes by nursing staff
Timepoint [1] 389588 0
at 6, 12, 18, 24 and 48 hours post surgery
Secondary outcome [2] 389894 0
Composite bleeding outcome using the Bleeding Academic Research Consortium (BARC4) criteria28 (intracranial bleeding within 48 hours; reoperation after closure of sternotomy; transfusion of greater than or equal to 5 units of whole blood or RBCs (excluding cell saver blood) within the 48 hour intra or post operative period; chest tube output greater or equal to 2litres within a 24 hour period
Timepoint [2] 389894 0
Until 48 hours post surgery obtained through accessing medical records
Secondary outcome [3] 391696 0
Number of units of blood in the first 6, 12, 18, 24, 48 hours and at ICU discharge
Timepoint [3] 391696 0
At 6, 12, 18, 24, 48 hours post surgery and at ICU discharge recorded in the medical notes
Secondary outcome [4] 391697 0
Volume of fluid resuscitation in the first 6, 12, 18, 24, 48 hours and at ICU discharge
Timepoint [4] 391697 0
At 6, 12, 18, 24, 48 hours post surgery and at ICU discharge recorded in the medical notes
Secondary outcome [5] 391698 0
Thromboelastogram (TEG) indices before and after platelet transfusion
Timepoint [5] 391698 0
collected up until 48 hours post surgery if results are available and recorded in the medical notes
Secondary outcome [6] 391699 0
Haemoglobin and platelet concentrations in the last measurement prior to ICU discharge ( as composite secondary outcome)
Timepoint [6] 391699 0
At ICU discharge - results recorded in medical notes
Secondary outcome [7] 391700 0
Immediate, short or medium term adverse effects; specifically incidence of DMSO toxicity; local wound infection; systemic infection; fever (incidence of temperature >39C at any point in the ICU stay); venous thromboembolism; arterial occlusion; acute coronary syndrome; need for surgical intervention; and acute respiratory distress syndrome.
Timepoint [7] 391700 0
Up to 90 days post surgery; information obtained by accessing medical records.
Secondary outcome [8] 391701 0
Duration of mechanical ventilation in the first 90 days postoperative
Timepoint [8] 391701 0
Up to 90 days post surgery and obtained through accessing medical records
Secondary outcome [9] 391702 0
Length of post operative stay in ICU
Timepoint [9] 391702 0
Up to ICU discharge. Information obtained through accessing medical records
Secondary outcome [10] 391703 0
ICU, hospital and 90-day mortality, analysed as both landmark and time-to-event data (as composite outcome)
Timepoint [10] 391703 0
At ICU discharge, hospital discharge and 90 days post surgery obtained by accessing medical records.
Secondary outcome [11] 391704 0
Total estimated healthcare cost, incorporating the cost of provision of platelets, calculating the difference between resources use and costs from hospital medical records.
Timepoint [11] 391704 0
Up to 90 days post surgery and at hospital discharge
Secondary outcome [12] 392702 0
Length of postoperative stay in hospital
Timepoint [12] 392702 0
Up to hospital discharge and obtained through medical records

Eligibility
Key inclusion criteria
1. Cardiac surgery patients identified preoperatively as having a high risk of platelet transfusion by either:
- the ACSePT risk prediction tool (score of 1 or higher) OR
- the judgement of the clinicians caring for the patient
2. Written informed consent obtained prior to surgery
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Aged less than 16 years
2. Females of child-bearing age (16- 55 years) who are RhD-negative or whose RhD status is unknown
3. Previous receipt of platelet transfusion during this hospital admission
4. DVT or PE first diagnosed within the preceding 6 months
5. More than one lifetime episode of DVT or PE
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>2 or
- aPTT > 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 enrolled in this trial
12. Previous enrolment in a clinical trial of a medication or technique thought to influence bleeding during this admission, with the exception of any trial of aspirin
13. Previous enrolment in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Study platelets will be supplied with an opaque bag that obscures their method of storage (cryopreserved or liquid-stored), concealing this information from blinded clinical and research staff and study participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised 1:1 to cryopreserved or standard platelets. Randomisation will be stratified by site and will be in variable block sizes.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All analyses will be performed on an intention-to-treat basis. Variables will be assessed for normality and transformed as appropriate. Group comparisons will be performed using chi-square tests for equal proportion, student t-tests or Wilcoxon rank sum tests as appropriate, with results reported as percentages (n), mean (standard deviation) and median (interquartile range) respectively. Hierarchical sensitivity analysis will be performed adjusting for site, baseline imbalance and known covariates using appropriate distribution-dependent regression (linear, median, logistic or proportional hazards).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2021
Actual
14/03/2022
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
228
Accrual to date
111
Final
Recruitment outside Australia
Country [1] 23280 0
New Zealand
State/province [1] 23280 0

Funding & Sponsors
Funding source category [1] 307379 0
Government body
Name [1] 307379 0
Health Research Council of New Zealand
Country [1] 307379 0
New Zealand
Primary sponsor type
Other
Name
Medical Research Institute of New Zealand
Address
Level 7, CSB Building
Wellington Hospital
Riddiford Street, Newtown,
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 308035 0
None
Name [1] 308035 0
Address [1] 308035 0
Country [1] 308035 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307465 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 307465 0
Ethics committee country [1] 307465 0
New Zealand
Date submitted for ethics approval [1] 307465 0
25/02/2021
Approval date [1] 307465 0
30/04/2021
Ethics approval number [1] 307465 0
21/STH/66

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107330 0
Dr Shay McGuinness
Address 107330 0
CVICU
Level 4, Building 32
Auckland City Hospital
2 Park Road
Grafton, Auckland 1023
Country 107330 0
New Zealand
Phone 107330 0
+64 21324771
Fax 107330 0
Email 107330 0
shaymc@adhb.govt.nz
Contact person for public queries
Name 107331 0
Leanlove Navarra
Address 107331 0
Medical Research Institute of New Zealand
Level 7, CSB Building
Wellington Hospital
Riddiford Street. Newtown
Wellington 6021
Country 107331 0
New Zealand
Phone 107331 0
+64 27 553 1488
Fax 107331 0
Email 107331 0
leanlove.navarra@mrinz.ac.nz
Contact person for scientific queries
Name 107332 0
Shay McGuinness
Address 107332 0
CVICU
Level 4, Building 32
Auckland City Hospital
2 Park Road
Grafton, Auckland 1023
Country 107332 0
New Zealand
Phone 107332 0
+64 21324771
Fax 107332 0
Email 107332 0
shaymc@adhb.govt.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No data sharing available at this time.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AICryopreserved platelets compared with liquid-stored platelets for the treatment of surgical bleeding: protocol for two multicentre randomised controlled blinded non-inferiority trials (the CLIP-II and CLIPNZ-II trials)2022https://doi.org/10.1136/bmjopen-2022-068933
N.B. These documents automatically identified may not have been verified by the study sponsor.