Extended Cold Stored Apheresis Platelets in Cardiac Surgery Patients (CHASE)

Evaluation of Efficacy and Safety of Extended Cold Stored Apheresis Platelets Versus Conventional Apheresis Platelets in Cardiac Surgery Patients

This trial is being performed to evaluate the feasibility of the study protocol and to test the efficacy and safety of platelets stored at cold conditions (1-6°C) in 100% plasma for 10-14 days (CSP) in cardiac surgery patients who are actively bleeding and require platelet transfusion.

Study Overview

• Status: Recruiting
• Conditions: Hemorrhage; Bleeding; Surgical Blood Loss; Platelets; Defect
• Intervention / Treatment: Biological: Cold stored platelets in 100% plasma stored for 10-14 days; Biological: Room temperature stored platelets in 100% plasma stored for up to 7 days

Detailed Description

Cardiac surgery featuring cardiopulmonary bypass (CPB) has a detrimental effect on platelet function. Contact with foreign surfaces causes a transient platelet dysfunction. The bleeding time is prolonged for the time on bypass and reverts to normal approximately one hour after cardiac surgery in uncomplicated cases. Hemorrhage following cardiac surgery with CPB can cause surgical re-exploration and increased mortality. The overall risk for surgical re-exploration is between 2.5-5%. Patients who undergo re-exploration due to excessive bleeding have a 2-6 fold increased mortality compared with non-bleeding patients. Storage of platelets at 1-6°C has the advantage of potentially prolonging storage times while reducing bacterial contamination. Room-temperature storage has led to a 5 day storage time limit since bacterial growth and septic reactions increase rapidly after 5-7 days. CSP were the standard of care in the 1960-70s. CSP were abandoned when a reduced platelet survival was observed in platelet radiolabeling studies. Nevertheless, CSP may have several advantages over RSP in the study population including a state of pre-activation and therefore a potentially superior hemostatic function. A small pilot trial investigating CSP in cardiac surgery patients in Norway found a non-significant trend towards improved bleeding control with CSP transfusions. However, data evaluating the in vivo efficacy of CSP is limited in scale and quality with mixed results. The investigators and others have shown that CSP have a superior function compared with RSP in vitro and more data are needed to clarify the relative efficacy of CSP in vivo. The investigators hypothesize that 1) CSP are more effective than RSP at reducing blood loss and improving platelet function in subjects actively bleeding due to cardiac surgery with cardiopulmonary bypass (CPB), and that 2) CSP are safe and do not lead to increased risks relative to RSP.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jeffrey Miles, M.S.; Phone Number: 206-689-6285; Email: jmiles@bloodworksnw.org
• Study Contact Backup: Name: Pat Klotz, BSN; Phone Number: 206-568-2238; Email: pklotz@bloodworksnw.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Swedish Medical Center - Cherry Hill
      • Contact: Inger Rasmussen; Phone Number: 206-215-3989; Email: inger.rasmussen@swedish.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Subject age is greater than or equal to 18 years of age.
• 2. Subject can speak and read English.
• 3. Subject weight is greater than 40 kg.
• 4. Subject is scheduled for redo, triple valve, or complex aortic cardiac surgery with cardiopulmonary bypass.
• 5. Subject has ability to comprehend and willingness to sign Informed Consent Form (ICF).
• 6. If female of childbearing potential, must have a negative pregnancy test and agree to use one of the following methods of contraception during the course of study participation: abstinence, intrauterine contraception device, hormonal method, or barrier method.
• 7. Subject agrees to not participate in another interventional study during study participation.
• 8. The clinical site can obtain both possible platelet products (CSP and RSP) as needed per the study protocol given the subject's anticipated surgery date.

Exclusion Criteria:

• 1. Subject has history of known repeated, severe transfusion reactions.
• 2. Subject requires washed products, volume reduced products, or products with additive solution.
• 3. Subject is planned to receive autologous or directed transfusions.
• 4. Subject has or is expected to require post-surgical ventricular assist device (VAD), hemodialysis, or extracorporeal membrane oxygenation (ECMO) within 24 hours of the Study Treatment Window.
• 5. Subject is thrombocytopenic (less than 100 x 103 platelets/μL) on most recent measurement.
• 6. Subject is pregnant or breastfeeding.
• 7. Subject is a prisoner
• 8. Subject has active infection.
• 9. Subject refuses blood products.
• 10. Subject has a history of unprovoked deep vein thrombosis (DVT) or unprovoked pulmonary embolism (PE).
• 11. Subject has previously been enrolled and received a study platelet transfusion.
• 12. Subject has known bleeding diathesis (hemophilia, Von Willebrand Disease, or others)
• 13. At discretion of subject's physician, Sub-Investigator (SI), or Principle Investigator (PI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cold stored platelets in 100% plasma stored for 10-14 days; Cold stored apheresis platelets in 100% plasma stored for 10-14 days, maximum of up to three units (3x10^11/unit) from the start of surgery until 24 hours after the end of surgery	Biological: Cold stored platelets in 100% plasma stored for 10-14 days; Subjects will receive cold stored platelets from the start of surgery until 24 hours after the end of surgery
Active Comparator: Room temperature stored platelets in 100% plasma stored for up to 7 days; Room temperature stored platelets in 100% plasma stored for up to 7 days, maximum of up to three units (3x10^11/unit) from the start of surgery until 24 hours after the end of surgery	Biological: Room temperature stored platelets in 100% plasma stored for up to 7 days; Subjects will receive room temperature stored platelets from the start of surgery until 24 hours after the end of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of the recruitment and accrual into the study protocol.	Number of subjects screened and enrolled into the study protocol.	24 hours following end of cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total allogeneic blood units transfused (RBCs only, platelets only, plasma only, and composite of all three)	Number of units	Start of surgery to 24 hours after surgery
Chest tube output volume	volume of chest tube output measured in milliliters.	24 hours after completion of surgery
Hemostatic agents administered	The total individual doses of hemostatic agents	24 hours after completion of surgery
Number of subjects requiring surgical re-exploration due to uncontrolled bleeding	binary	24 hours after completion of surgery
Number of subjects with evidence of new infection or sepsis	per protocol definition	Through post-op day 3
Number of subjects with evidence of a thrombotic event	per protocol definition	Through study completion, an average of 3 weeks.
Number of subjects with evidence of liver injury.	Maximum post-operative change from pre-surgical baseline within the first three days	Through post-op day 3
Hospital free days	Number of days out of the hospital.	Post-op through day 28.
ICU free days	Number of days out of the ICU	Post-op through day 28.
Ventilator free days	Number of days not on a ventilator.	post-op through day 28.
Mortality	To evaluate mortality at 28 days.	Post-op through day 28.

Collaborators and Investigators

• Sponsor: Moritz Stolla, MD
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Moritz Stolla, MD, Bloodworks Northwest

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Estimated): October 29, 2024
• Study Completion (Estimated): October 29, 2024

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Intraoperative Complications; Hemorrhage; Blood Loss, Surgical
• Other Study ID Numbers: 2021-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No