ANZICS CTG Endorsed Study
CLIP II
A phase III multicentre blinded randomised controlled clinical non-inferiority trial of cryopreserved platelets vs. conventional liquid-stored platelets for the management of post-surgical bleeding. The cryopreserved vs. liquid platelets trial
Study Description
For logistic reasons and in order to use this scarce resource optimally, liquid-stored platelets with a shelf-life of 5 days are not stored in smaller hospitals. Cryopreservation in dimethylsulphoxide (DMSO) is a promising technology that would allow smaller hospitals to provide platelet transfusions, reduce overall wastage, and possibly produce better haemostasis.
The aim of this phase III clinical trial is to assess the efficacy, safety and cost effectiveness of cryopreserved platelets, compared to conventional liquid-stored platelets, for treatment of surgical bleeding.
Approximately 808 cardiac surgical patients at high risk of platelet transfusion will be recruited. Of these, it is expected that 202 will be transfused study platelets. A maximum of 3 units of study platelets will be given, after which open-label liquid stored platelets will be used.
Primary Endpoint:
- Volume of post-surgical bleeding in the first 12 hours from the time the surgeon starts to close the wound (non-inferiority design with a 20% / 200ml non-inferiority margin)
Major Secondary Endpoints:
- Requirement for postoperative blood products
- Volume of postoperative fluid resuscitation
- Immediate, short term or medium term adverse effects, especially DMSO toxicity, infection, venous thromboembolism, arterial occlusion, need for surgical intervention, and acute respiratory distress.
- ICU and hospital length of stay
- Total estimated healthcare cost
- 28-day mortality
Management Committee
Michael Reade (Chair), Denese Marks (Deputy Chair; lead blood scientist), Michael Bailey, Paul Bannon, Richard Charlewood, Glenn Eastwood, Craig French, David Gattas, Lisa Higgins, Anthony Holley, Raymond Hu, David Irving, Lacey Johnson, Shay McGuiness, Zoe McQuilten, Alistair Royse, Julian Smith, Laurence Weinberg, Erica Wood.
Project Manager
Belinda Howe
Administering Institution
ANZIC Research Centre, Monash University
Collaborators
ANZCA CTN
Australian Red Cross Blood Service
NZ Blood Service
Sample Size
808 patients randomised for 202 patients transfused
Funding
NHMRC Project Grant $1.825M
Project Status as of June 2019
The protocol has been finalised and submitted for HREC approval. The CRF has been translated into a format that can be uploaded as an eCRF. The study has been registered on ClinicalTrials.gov. (NCT03991481)
A DSMC Chair has been appointed (Dr Duncan Young, Oxford), and a draft DSMC charter is nearing final approval by the study management committee.
The website provider is preparing the eCRF, randomisation and general study information website.
The ARCBS are preparing material required for GMP certification of their platelet manufacturing capability, and anticipate having trial platelets ready before the end of 2019.
Study site selection depends on obtaining data on cardiac surgery case numbers and platelet transfusion rates from the ANZSCTS database. Likely high volume sites are being approached in advance of this data being available. Preliminary training material for hospital blood bank staff is being prepared by the ARCBS.
The approach to NZ participation in both CLIP-I (still recruiting in NZ) and CLIP-II has been finalised. CLIP-I will continue until there are sufficient patients to support an application for independent grant funding to support NZ participation in CLIP-II. NZ sites will use the slightly different protocol for platelet preparation developed by the NZ Blood Service in CLIP-II, subject to their ability to participate, which is dependent on funding. They will recruit to the same sample size (approx. 808 randomised for 202 transfused) as the Australian sites, using identical CRFs, which will facilitate a comparison of platelet manufacturing techniques.
Reference
CTG1718-06
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