The Cryopreserved vs. Liquid Platelets Trial (CLIP II)

Australian and New Zealand Intensive Care Research Centre

Status and phase: Active, not recruiting; Phase 3

Conditions: Surgical Blood Loss; Hemorrhage

Treatments: Biological: Liquid-stored platelets; Biological: Cryopreserved platelets

Study type: Interventional

Funder types: Other

Identifiers

NCT03991481

ANZIC-RC/MR002

Details and patient eligibility

About

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.

Full description

For logistic reasons and in order to use this scarce resource optimally, liquid-stored platelets are not stored in smaller hospitals, or in deployed military hospitals. Patients in these hospitals therefore currently have limited or no access to platelet transfusion. Cryopreservation of platelets is a promising technology that would allow smaller hospitals to provide platelet transfusions, reduce overall platelet wastage, and possibly produce better patient outcomes through more effective haemostasis.

This 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. The study will recruit patients in Australian tertiary hospitals.The study hypothesis is that cryopreserved platelets will be at least as effective as conventional liquid-stored platelets in the treatment of active bleeding due to surgery.

Enrollment: 388 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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

2. Written informed consent obtained prior to surgery

Exclusion criteria

1. Aged less than 18 years

2. Females of child-bearing age (18- 55 years) who are RhD (Rhesus type D)-negative or whose RhD (Rhesus type D) status is unknown

3. Receipt of platelet transfusion during this hospital admission

4. Deep Vein Thrombosis or Pulmonary Emboli first diagnosed within the preceding 6 months

5. More than one lifetime episode of Deep Vein Thrombosis or Pulmonary Emboli

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 (International Normalised Ratio) >2 or
   • aPTT (Activated Partial Thromboplastin Time) > 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 randomised in this trial

12. 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.

13. Previous enrolment in this study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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388 participants in 2 patient groups

Cryopreserved platelets

Experimental group

Description:

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

Treatment:

Biological: Cryopreserved platelets

Liquid-stored platelets

Active Comparator group

Description:

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

Treatment:

Biological: Liquid-stored platelets