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).

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Corporate Authors:
      CLIP-II and CLIPNZ-II Investigators.; CLIP-II and CLIPNZ-II Investigators
    • Source:
      Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BMJ Publishing Group Ltd, 2011-
    • Subject Terms:
      Anticoagulants*/therapeutic use ; Blood Loss, Surgical*/prevention & control; Humans ; Australia ; Blood Platelets ; Cryopreservation ; Multicenter Studies as Topic ; Equivalence Trials as Topic ; Randomized Controlled Trials as Topic
    • Abstract:
      Introduction: Cryopreservation at -80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries.
      Methods and Analysis: CLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change in clinical practice. Cost-effectiveness analyses will be incorporated into each study such that, should clinical non-inferiority compared with standard care be demonstrated, the hospitals in each country that would benefit most from changing to a cryopreserved platelet blood bank will be known.
      Ethics and Dissemination: CLIP-II was approved by the Austin Health Human Research Ethics Committee (HREC/54406/Austin-2019) and by the Australian Red Cross Lifeblood Ethics Committee (2019#23). CLIPNZ-II was approved by the New Zealand Southern Health and Disability Ethics Committee (21/STH/66). Eligible patients are approached for informed consent at least 1 day prior to surgery. There is no provision for consent provided by a substitute decision-maker. The results of the two trials will be submitted separately for publication in peer-reviewed journals.
      Trial Registration Numbers: NCT03991481 and ACTRN12621000271808.
      Competing Interests: Competing interests: MCR is a serving officer in the Australian Defence Force, which intends to operationalise cryopreserved platelets if the trial shows favourable results. DCM and LJare employed by Australian Red Cross Lifeblood, and RC is employed by the NZ Blood Service, which could both adopt cryopreserved platelets if the trial shows cost effectiveness. Other authors declare no conflicts of interest.
      (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
    • References:
      Transfusion. 1999 Aug;39(8):880-8. (PMID: 10504125)
      Thromb Res. 1990 Mar 15;57(6):919-24. (PMID: 2382258)
      Vox Sang. 2002 Nov;83(4):347-51. (PMID: 12437522)
      BMJ. 2010 Mar 23;340:c869. (PMID: 20332511)
      J Thorac Cardiovasc Surg. 1999 Jan;117(1):172-83; discussion 183-4. (PMID: 9869772)
      Transfus Apher Sci. 2015 Oct;53(2):146-52. (PMID: 26549672)
      JAMA. 2012 Jun 20;307(23):2526-33. (PMID: 22797452)
      Transfusion. 2020 Oct;60(10):2272-2283. (PMID: 32757209)
      Ann Intern Med. 2013 Feb 5;158(3):200-7. (PMID: 23295957)
      Prog Clin Biol Res. 1982;88:165-80. (PMID: 7100208)
      Vox Sang. 2022 Mar;117(3):337-345. (PMID: 34581452)
      Blood. 2012 Jun 7;119(23):5553-62. (PMID: 22496156)
      Transfusion. 2006 Jul;46(7):1120-9. (PMID: 16836558)
      Cryobiology. 2011 Apr;62(2):100-6. (PMID: 21241687)
      Vox Sang. 2017 Oct;112(7):684-688. (PMID: 28929502)
      Eur J Cardiothorac Surg. 2012 Apr;41(4):734-44; discussion 744-5. (PMID: 22378855)
      Transfusion. 2019 Apr;59(S2):1474-1478. (PMID: 30980747)
      Asian J Transfus Sci. 2007 Jan;1(1):8-11. (PMID: 21938226)
      BMJ. 2002 Sep 21;325(7365):652-4. (PMID: 12242181)
      PLoS One. 2016 Dec 13;11(12):e0168401. (PMID: 27959967)
      Transfusion. 2016 Oct;56(10):2455-2465. (PMID: 27600298)
      Transfus Apher Sci. 2006 Jun;34(3):289-98. (PMID: 16815757)
      Transfusion. 2005 Apr;45(4):596-603. (PMID: 15819682)
      Transfusion. 2015 Apr;55(4):838-47. (PMID: 25371169)
      Transfusion. 2019 Sep;59(9):2794-2804. (PMID: 31290573)
      Circulation. 2011 Jun 14;123(23):2736-47. (PMID: 21670242)
    • Contributed Indexing:
      Investigator: MC Reade; DC Marks; B Howe; Z McQuilten; C French; L Weinberg; D Irving; E Wood; L Johnson; P Bannon; D Gattas; G Eastwood; A Royse; J Smith; R Hu; A Holley; A Higgins; S McGuinness; R Parke; E Gilder; K Byrne; R Charlewood; S Galvin; K Hayes; J Moore; S Morley; C Walker; MC Reade; L Navarra; B Howe
      Keywords: Adult anaesthesia; Adult intensive & critical care; Blood bank & transfusion medicine; Cardiac surgery
    • Molecular Sequence:
      ClinicalTrials.gov NCT03991481
    • Accession Number:
      0 (Anticoagulants)
    • Publication Date:
      Date Created: 20230105 Date Completed: 20230110 Latest Revision: 20230111
    • Publication Date:
      20231215
    • Accession Number:
      PMC9772641
    • Accession Number:
      10.1136/bmjopen-2022-068933
    • Accession Number:
      36600425