Cryopreserved vs Liquid-Stored Platelets for the Treatment of Surgical Bleeding: The CLIP-II Randomized Noninferiority Clinical Trial

Abstract

Importance: Liquid-stored platelets have a shelf-life of 5 to 7 days, limiting availability and resulting in wastage.

Objective: To assess the effectiveness and safety of dimethyl sulfoxide-cryopreserved platelets, which have a shelf-life of 2 years, as a treatment for cardiac surgery bleeding.

Design, setting, and participants: The Cryopreserved vs Liquid Platelets II (CLIP-II) trial was a multicenter, randomized, double-blind, parallel-group noninferiority trial, which enrolled patients between August 2021 and April 2024 at 11 Australian tertiary hospitals, with follow-up completed in July 2024. Patients at high risk of platelet transfusion were eligible. Patients were excluded if they had a history of deep vein thrombosis or pulmonary embolism, were coagulopathic, or were females aged 18 to 55 years who were rhesus D (RhD) negative or of unknown RhD status. Of 879 patients meeting inclusion criteria, 182 were excluded and 285 did not consent, leaving 412. Of these, 388 were randomized and 202 received study platelets.

Interventions: Patients received up to 3 units of either group O cryopreserved platelets or conventional liquid-stored platelets, commencing intraoperatively or in the first 24 postoperative hours.

Main outcomes and measures: The primary outcome was postsurgical chest drain bleeding within the first 24 hours following intensive care unit admission. Noninferiority was defined prospectively as less than 20% greater bleeding in this period. Five secondary and 42 tertiary outcomes were defined a priori.

Results: Of the 202 transfused patients (mean [SD] age, 64.4 [13] years; 75.7% male), 61 (30.2%) underwent nonelective surgery. The primary outcome did not differ between groups (605 mL in cryopreserved platelet group vs 535 mL in liquid-stored platelet group; ratio of geometric means [cryopreserved to liquid ratio], 1.13 [95% CI, 0.96-1.34]; P = .07). As the confidence interval includes bleeding exceeding the noninferiority margin, noninferiority was not established. Cryopreserved platelet transfusion was associated with higher intraoperative and total perioperative blood loss (ratio of geometric means [cryopreserved to liquid ratio], 1.42 [95% CI, 1.12-1.80]; 1.31 [95% CI, 1.07-1.60], respectively), and increased red cell, plasma, and cryoprecipitate transfusion. While there were no differences in the incidence of prespecified adverse events, patients receiving cryopreserved platelets experienced longer times to extubation and intensive care unit/hospital discharge (median [IQR] duration of ventilation, 25.5 hours [16.1-77.3] vs 23.6 hours [13.1-52.8]; median [IQR] intensive care unit length of stay, 3.8 days [2.0-6.0] vs 3.0 days [1.9-4.9]; median hospital length of stay, 10.9 days [7.87-17.0] vs 9.1 [6.9-14.9]).

Conclusions and relevance: Cryopreserved platelets did not meet the predefined threshold for noninferiority in hemostatic effectiveness at 24 hours after ICU admission. Additional predefined end points consistently indicated diminished hemostatic effectiveness, although prespecified adverse events were comparable.

Trial registration: ClinicalTrials.gov Identifier: NCT03991481.