The Cryopreserved vs. Liquid Platelets Trial

NCT03991481 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: ANZIC-RC/MR002
• Study Type: interventional
• Target: 388
• Locations: 1 country
• Sites: 6

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.

Conditions

Surgical Blood Loss; Hemorrhage

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Total volume of post-surgical chest drain bleeding

  From ICU admission up to removal of drains, death or day 28, whichever occurs first

• Composite bleeding outcome using the BARC4 criteria

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

• 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

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

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

Other Outcomes (28)

• 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

• 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

Study Arms (2)

Cryopreserved platelets

EXPERIMENTAL

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

Biological: Cryopreserved platelets

Liquid-stored platelets

ACTIVE COMPARATOR

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

Biological: Liquid-stored platelets

Interventions

Cryopreserved platelets BIOLOGICAL

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

Cryopreserved platelets

Liquid-stored platelets BIOLOGICAL

Liquid-stored platelets as per standard practice

Liquid-stored platelets

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Australian and New Zealand Intensive Care Research Centre: lead
• Australian Red Cross: collaborator

Study Sites (6)

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

The Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Townsville Hospital

Douglas, Queensland, 4814, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Related Publications (2)

• Reade MC, Marks DC, Howe BD, Bailey MJ, Bannon PG, Eastwood GM, French CJ, Gattas DJ, Higgins AM, Holley AD, Hu RT, Irving DO, Johnson L, McGuinness SP, McQuilten ZK, Royse AG, Smith JA, Weinberg L, Wood EM; Cryopreserved vs Liquid Platelets II (CLIP-II) Investigators, the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australasian Society of Car; Cryopreserved vs Liquid Platelets II (CLIP-II) Investigators, the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australasian Society of Cardiac and Thoracic Surgeons. Cryopreserved vs Liquid-Stored Platelets for the Treatment of Surgical Bleeding: The CLIP-II Randomized Noninferiority Clinical Trial. JAMA. 2025 Dec 8:e2523355. doi: 10.1001/jama.2025.23355. Online ahead of print.

  PMID: 41360717 DERIVED

• Reade MC, Marks DC, Howe B, McGuinness S, Parke R, Navarra L, Charlewood R, Johnson L, McQuilten Z; CLIP-II and CLIPNZ-II Investigators.; CLIP-II and CLIPNZ-II Investigators. Cryopreserved 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). BMJ Open. 2022 Dec 20;12(12):e068933. doi: 10.1136/bmjopen-2022-068933.

  PMID: 36600425 DERIVED

MeSH Terms

Conditions

Blood Loss, Surgical; Hemorrhage

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Study Officials

• Michael Reade

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: June 19, 2019
• Study Start: August 17, 2021
• Primary Completion: July 17, 2024
• Study Completion: November 1, 2025
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

AU (6)