DMSO Cryopreserved Platelets in Cardiopulmonary Bypass Surgery (CRYPTICS)

Study Overview
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Brief Summary
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A randomized, parallel group, active comparator-controlled trial to evaluate the non-inferiority or superiority of Cryopreserved Platelets with Liquid Stored Platelets in controlling blood loss in patients undergoing Cardiopulmonary Bypass Surgery.

Detailed Description
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A randomized, parallel group, active comparator-controlled trial to evaluate the non-inferiority or superiority of Cryopreserved Platelets with Liquid Stored Platelets in controlling blood loss in patients undergoing Cardiopulmonary Bypass Surgery. Patients planning to undergo Cardiopulmonary Bypass Surgery with risk factors for significant bleeding post-surgery will be approached. Subjects will be randomized in a 1:1 ratio to receive either Cryopreserved Platelets or Liquid Stored Platelets. Eligible subjects will undergo Cardiopulmonary Bypass Surgery and at the completion of bypass and heparin reversal subjects will likely be assessed for eligibility before coming off bypass. Study platelets will be given either intraoperatively after heparin reversal and return of active clotting time (ACT) to < 140 sec or post operatively (after chest closure). A single interim analysis is planned after 150 subjects are treated (75 in each treatment arm) to assess whether the study can be stopped for overwhelming efficacy or if an increase in sample size is warranted to maintain desired conditional power.

Official Title
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Randomized Controlled Trial Comparing Dimethyl Sulfoxide Cryopreserved Platelets to Liquid Stored Platelets in Patients Undergoing Cardiopulmonary Bypass Surgery (CRYPTICS)

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Biological: Human platelets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, at least 18 years of age Undergoing CPB surgery with at least one risk factor for post-surgical bleeding including: All re-operative cardiac procedures. Expected bypass > 120 minutes. Any combined cardiac surgery procedures (e.g. multiple valve, valve/CABG). Any procedure that in the estimation of the surgical attending, has a high likelihood of receiving platelets Ability to comprehend and willingness to sign informed consent. If female of childbearing potential, have a negative pregnancy test on the day of the surgery and prior to the surgery agrees to use a method of highly effective birth control from the time of consent through the end of the safety follow-up period (Day 6 or discharge from hospital, whichever is earlier). Note: women must have been surgically sterilized [bilateral tubal ligation, bilateral oophorectomy, total hysterectomy) or postmenopausal (≥50 years of age and continuous amenorrhea for 24 months) to be considered non-childbearing potential. Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from the study: Undergoing any of the following surgical procedures: Coronary artery bypass surgery alone Implantation of ventricular assist device Thoracoabdominal aortic aneurysm repair Known or suspected pregnancy or breastfeeding History of any major unprovoked thrombotic events History of heparin-inducted thrombocytopenia Active infection treated with antibiotics Refuse transfusion of blood products for religious or other reasons Previous enrollment in this study Immune thrombocytopenic purpura Known allergy to DMSO In the judgement of the investigator, is not a good candidate for the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, parallel group, active comparator-controlled trial to evaluate the noninferiority or superiority of CPP with LSP in controlling blood loss in patients undergoing CPB surgery.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cryopreserved platelets<br>Cryopreserved platelets to be given intraoperatively or post operatively up to 3 units post-heparin reversal | Biological: Human platelets<br>* Platelets given to control bleeding<br>|
| Active Comparator: Liquid stored platelets<br>Liquid stored platelets to be given intraoperatively or post operatively up to 3 units post-heparin reversal | Biological: Human platelets<br>* Platelets given to control bleeding<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint assessed from time zero until the drain tubes are removed or 24 hours post time zero. | Total volume of chest tube drainage assessed by measurement of the volume of blood collected from the mediastinal and pleural drains from time zero, the time of 1) chest closure or equivalent, 2) chest tubes or equivalent are attached to a graduated post drainage system, and 3) with suction (defined as time zero for analytical purposes) until the drain tubes are removed or 24 hours post time zero, whichever is earlier. | From time zero until the drain tubes are removed or 24 hours post time zero, whichever is earlier | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoint assessed from time zero until the drain tubes are removed or 24 hours post time zero. | The primary endpoint given in mL/kg | From time zero until the drain tubes are removed or 24 hours post time zero, whichever is earlier | 
| Secondary Efficacy Endpoint assessed at 6 hours interval through 24 hours post time zero or when the chest tubes are removed. | Chest tube drainage volume (mL) collected at 6 hours intervals through 24 hours post time zero or tube removal, whichever is earlier. | 6 hours intervals through 24 hours post time zero or when chest tubes are removed, whichever is earlier. | 
| Secondary Efficacy Endpoint at 6 hours intervals through 24 hours post time zero or when chest tubes are removed | Drainage rate (mL/hr) collected at 6 hours intervals through 24 hours post time zero or when chest tube are removed, whichever is earlier. | 6 hours intervals through 24 hours post time zero or when chest tubes are removed, whichever is earlier | 
| Secondary Efficacy Endpoint assessed at the end of first study platelet transfusion through 24-hour post heparin reversal (Efficacy follow-up period) | Total units by type of other post-operative blood products (pRBC, non-study platelets, CRYO, plasma, clotting factor concentrates) infused after the end of the first study platelet transfusion until end of the efficacy follow-up period | Infused after the end of the first study platelet transfusion through 24-hour post heparin reversal (Efficacy follow-up period) | 
| Secondary Efficacy Endpoint assessed within 24 hour post heparin reversal (Efficacy follow-up period) | Incidence of surgical re-exploration and incidence of verified surgical or other causes for bleeding within the 24 hour period after heparin reversal | Within the 24 hour period after heparin reversal | 
| Secondary Efficacy Endpoint assessed from first protamine administration to the time of first suture for incision closure on Day 1 (Day of Surgery) | Time to hemostasis (defined as the time from first protamine administration to the time when the surgeon initiates the first suture for incision closure) | Time from first protamine administration to the time when the surgeon initiates the first suture for incision closure, Day 1 (Day of operation) | 
| Secondary Efficacy Endpoint assessed at the first study platelet transfusion through 24-hour post heparin reversal (Efficacy follow-up period) | Treatment failure (defined as requiring more than three units of study treatment (CPP or LSP)) | Time of first study platelet transfusion through 24-hour post heparin reversal (Efficacy follow-up period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryopreserved Platelets