Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen to Expedite Product Availability in Perioperative Bleeding

Pilot Clinical Trial of Transfusion of Pathogen Reduced Cryoprecipitated Fibrinogen (INTERCEPT Fibrinogen Complex) in Patients With Bleeding to Expedite Product Availability and Improve Outcomes in Perioperative Bleeding

The goal of this quality improvement study is to compare pathogen-reduced cryoprecipitate with traditional cryoprecipitate in liver transplant and cardiovascular patients. The investigators hypothesize that by having immediate access to a readily available thawed blood product that replaces fibrinogen (the main substrate of a blood clot), early bleeding can be treated before it escalates into uncontrolled hemorrhage, and therefore additional blood products, like platelets, plasma and red blood cells can be avoided.

Participants will be given one of the two FDA-approved blood products.

Study Overview

• Status: Completed
• Conditions: Bleeding; Hypofibrinogenemia
• Intervention / Treatment: Biological: Traditional Cryoprecipitate; Biological: Pathogen-Reduced Cryoprecipitate

Detailed Description

Immediately replacing fibrinogen in perioperative bleeding patients with acquired fibrinogen deficiency improves outcomes. The product that is primarily used for fibrinogen replacement in the US, cryoprecipitate (cryo), must be stored frozen and expires six hours after thawing, resulting in a delay in transfusion of approximately 50 minutes from the time it is ordered, as well as unnecessary transfusion of more readily available but not indicated blood components that are transfused while the patients waits for cryo . A modified version of the product, pathogen reduced (PR) cryo, is now FDA approved and can be thawed and stored for 5 days, allowing the product to be available immediately when needed. In this quality improvement study, the investigators will compare the effect that readily available, pre-thawed PR cryo has on transfusion practice in cardiovascular and liver transplant patients who receive PR cryo versus those who receive traditional cryo by randomizing cryo transfusions in the blood bank by month to all cryo or all PR cryo. All clinical decisions, including the need for cryo, and laboratory testing will occur per standard of care.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • New York-Presbyterian Hospital/Weill Cornell Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adult patients undergoing cardiovascular surgery or liver transplant who receive cryo during surgery during the two year study period.

2. Cardiovascular surgery includes the following procedures:

   1. coronary artery bypass grafting
   2. valve repair or replacement
   3. open thoracic aortic and thoracoabdominal aortic surgery
   4. atrial or ventricular septal defects
   5. ventricular assist device implantation or revision
   6. or any combination of the above.

Exclusion Criteria:

1. Patients who do not receive any cryo product in the OR
2. Patients who are not cardiovascular surgery or liver transplant patients
3. Cardiac transplantation surgery
4. Patients who receive a product in error within either the cryo time period or the PR cryo time period. For example, PR cryo during a cryo month or cryo during a PR cryo time month.
5. Patients who receive less than 1 pool (5 units) of cryo
6. Pediatric patients (less than 18 years of age).
7. Patients who received both PR cryo and traditional cryo
8. Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patients given Traditional Cryo; These are the liver transplant and cardiothoracic (LT and CT) patients that will be given traditional cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month.	Biological: Traditional Cryoprecipitate; This is the cryoprecipitate already currently being given to patients with a cryo order.
Experimental: Patients given PR Cryo; These are the liver transplant and cardiothoracic (LT and CT) patients that will be given PR cryo based on the randomization protocol. The blood bank will alternate use of PR cryo and regular cryo each month for all patients with a cryo order. All patients will receive either traditional cryo or PR cryo in a given month.	Biological: Pathogen-Reduced Cryoprecipitate; This is the pathogen-reduced cryoprecipitate that is intended to be compared to the standard cryoprecipitate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of RBCs Used Over Admission	RBCs used over admission	Within the first 30 days after surgery.
Total Number of Platelets Used Over Admission	Plts used over admission	Within the first 30 days after surgery.
Total Number of Plasma Used Over Admission	All units over admission	Within the first 30 days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cryo Units Used Perioperatively	All products within 3 days	3 days post procedure
Number of RBCs Used Perioperatively	Number of RBC units transfused during perioperative period	3 days post procedure
Number of Plasma Used Perioperatively		3 days post procedure
Number of Platelets Used Perioperatively	Number of platelet units transfused during perioperative period	3 days post procedure
Time From Operating Room (OR) Start Time to Start of Cryo Transfusion		procedure (Time from OR start time to start of cryo transfusion)
Time From Cryo Order to Start of Transfusion	Time to cryo order time to start of cryo transfusion	procedure (Time from cryo order to start of transfusion)
Number of Cryo Units Wasted by Blood Bank	This captures the Cryoprecipitate units discarded.	Daily, up to approximately 24 months
Pre Transfusion FIBTEM Amplitude 10 Min After Start of Clot Formation	FIBTEM before transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding.	Variable, but it is generally available within 15 minutes of the start of ROTEM testing.
Post Transfusion FIBTEM Amplitude at 10 Min After Start of Clot Formation	FIBTEM after transfusion, if anesthesiologist orders it. FIBTEM is a point of care laboratory test measuring fibrinogen contribution to a clot. It is part of ROTEM testing and helps providers determine if patients need fibrinogen supplementation during surgical bleeding.	Variable, but it is generally available within 15 minutes of the start of ROTEM testing.
Maximum Clot Firmness (MCF)	The maximum strength of a clot as determined by ROTEM testing.	Variable, but it is generally available within 1 hour of the start of ROTEM testing.
Pre-transfusion Fibrinogen Level	The fibrinogen measurement before cryoprecipitate is transfused.	During surgery, within 3 hours of specimen receipt by laboratory.
Highest Fibrinogen Level Within 24 Hours		Within 24 hours after surgery
Lowest Fibrinogen Level Within 24 Hours		Within 24 hours after surgery
Cumulative Volume in Drains After Surgery (e.g., Chest Tube for CV Surgery) at the Time of Removal	The cumulative volume in drains after surgery (e.g., chest tube for CV surgery) at the time of drain removal	Up to approximately 3 days
Volume in Drains (Chest Tube for CV Surgery)		At 24 hours after surgery
Time From End of Bypass Pump for CV Surgery		Until end of surgery
Length of Stay in OR	Operating room length of stay	Duration of time in operating room
Length of Stay in ICU	Participant length of stay in ICU setting	During hospitalization, approximately 5 days to 30 days
Length of Stay in Hospital	Overall length of stay in hospital	During hospitalization, approximately 5 days to 30 days
Need for Ventilator		During hospitalization, approximately 5 days to 30 days
Time on Ventilator	If participant was on ventilator, amount of time spent on ventilator	During hospitalization, approximately 5 days to 30 days
Overall Cost of Cryo vs PR Cryo, When Factoring Wastage	Cost of traditional cryoprecipitate compared to PR Cryoprecipitate.	Daily, approximately 24 months
Number of Participants That Experienced an Adverse Event of Fever	All participants that experience fevers that occur during the time frame	Within 5 days of surgery start time
Number of Participants That Experienced an Adverse Event of Infection	All participants that experience infections that occur during the time frame	Within 5 days of surgery start time
Number of Participants That Experienced an Adverse Event of Transfusion Reaction.	All participants that experience transfusion reactions that occur during the time frame	Within 5 days of surgery start time
Fibrinogen Level	Fibrinogen level most proximal to the end of surgery	Most proximal to end of procedure

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Cerus Corporation
• Investigators: Principal Investigator: Melissa Cushing, Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Arnup SJ, Forbes AB, Kahan BC, Morgan KE, McKenzie JE. Appropriate statistical methods were infrequently used in cluster-randomized crossover trials. J Clin Epidemiol. 2016 Jun;74:40-50. doi: 10.1016/j.jclinepi.2015.11.013. Epub 2015 Nov 26.
• Saland LC. Effects of reserpine administration on the fine structure of the rat pars intermedia. Cell Tissue Res. 1978 Nov 9;194(1):115-23. doi: 10.1007/BF00209237.
• Cushing MM, Fitzgerald MM, Harris RM, Asmis LM, Haas T. Influence of cryoprecipitate, Factor XIII, and fibrinogen concentrate on hyperfibrinolysis. Transfusion. 2017 Oct;57(10):2502-2510. doi: 10.1111/trf.14259. Epub 2017 Jul 21.
• Cushing MM, Haas T, Karkouti K, Callum J. Which is the preferred blood product for fibrinogen replacement in the bleeding patient with acquired hypofibrinogenemia-cryoprecipitate or fibrinogen concentrate? Transfusion. 2020 Jun;60 Suppl 3:S17-S23. doi: 10.1111/trf.15614. Epub 2020 Jun 1.
• Fenderson JL, Meledeo MA, Rendo MJ, Peltier GC, McIntosh CS, Davis KW, Corley JB, Cap AP. Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures. Transfusion. 2019 Apr;59(S2):1560-1567. doi: 10.1111/trf.15180.
• Bulkley GB, Wheaton LG, Strandberg JD, Zuidema GD. Assessment of small intestinal recovery from ischemic injury after segmental, arterial, venous, and arteriovenous occlusion. Surg Forum. 1979;30:210-3. No abstract available.
• Hsien S, Dayton JD, Chen D, Stock A, Bacha E, Cushing MM, Nellis ME. Hemostatic efficacy of pathogen-reduced platelets in children undergoing cardiopulmonary bypass. Transfusion. 2022 Feb;62(2):298-305. doi: 10.1111/trf.16768. Epub 2021 Dec 13.
• Lokhandwala PM, O'Neal A, Patel EU, Brunker PAR, Gehrie EA, Zheng G, Kickler TS, Ness PM, Tobian AAR. Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing. Transfusion. 2018 May;58(5):1126-1131. doi: 10.1111/trf.14550. Epub 2018 Feb 25.
• Thomson C, Sobieraj-Teague M, Scott D, Duncan E, Abraham S, Roxby D. Extending the post-thaw viability of cryoprecipitate. Transfusion. 2021 May;61(5):1578-1585. doi: 10.1111/trf.16366. Epub 2021 Mar 17.
• Cushing MM, Cohen T, Fitzgerald MM, Rand S, Sinfort A, Chen D, Keltner N, Ong S, Parra P, Benabdessadek D, Jimenez A, Haas T, Lau C, Girardi NI, DeSimone RA. Trial Of Pathogen-reduced Cryoprecipitate vs. Cryoprecipitated AHF to Lower Operative Transfusions (TOP-CLOT): study protocol for a single center, prospective, cluster randomized trial. Trials. 2024 Sep 27;25(1):625. doi: 10.1186/s13063-024-08398-x.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 3, 2025

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Cryoprecipitate; Pathogen Reduced Cryoprecipitate
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemorrhage; Afibrinogenemia
• Other Study ID Numbers: 22-04024649

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
• product manufactured in and exported from the U.S.: No